[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Next Article in Journal
Application of Metal Oxide Nanoparticles in Different Carcinomas
Previous Article in Journal
Exploring the Role of Fibroblasts in Promoting Neuroblastoma Cell Migration and Invasion
You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled.
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
JNT
Volume 5
Issue 4
10.3390/jnt5040014
jnt-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Advances in Photothermal and Photodynamic Nanotheranostics for Precision Cancer Treatment

by
Hossein Omidian
* and
Sumana Dey Chowdhury
Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA
*
Author to whom correspondence should be addressed.
J. Nanotheranostics 2024, 5(4), 228-252; https://doi.org/10.3390/jnt5040014
Submission received: 22 November 2024 / Revised: 6 December 2024 / Accepted: 10 December 2024 / Published: 13 December 2024
(This article belongs to the Topic Application of Nanomaterials and Nanobiotechnology in Cancer)
Browse Figures
Figure 1
<p>Schematic representation of the fabrication process of HA-IR808-SWNHs and the programmed treatment of tumors. Reprinted with permission from Ref. [<a href="#B39-jnt-05-00014" class="html-bibr">39</a>]. 2022, Elsevier.</p> "> Figure 2
<p>Imaging-guided photothermal-triggered immunotherapy using magnetic-responsive nanoagents (MINPs) stimulates immune responses to target both primary and distant untreated tumors. Reprinted with permission from Ref. [<a href="#B62-jnt-05-00014" class="html-bibr">62</a>], 2019, Elsevier.</p> "> Figure 3
<p>Schematic illustration of the design and preparation of Cy7-TCF-SS-NLG PNAs for synergistic treatments, which include photothermal therapy and checkpoint blockade immunotherapy. Reprinted with permission from Ref. [<a href="#B71-jnt-05-00014" class="html-bibr">71</a>], 2024, Elsevier.</p> ">
Versions Notes

Abstract

:
Nanotheranostics, combining photothermal therapy (PTT) and photodynamic therapy (PDT), can transform precision cancer treatment by integrating diagnosis and therapy into a single platform. This review highlights recent advances in nanomaterials, drug delivery systems, and stimuli-responsive mechanisms for effective PTT and PDT. Multifunctional nanoparticles enable targeted delivery, multimodal imaging, and controlled drug release, overcoming the challenges posed by tumor microenvironments. Emerging approaches such as hybrid therapies and immune activation further enhance therapeutic efficacy. This paper discusses the limitations of nanotheranostics, including synthesis complexity and limited tissue penetration, and explores future directions toward biocompatible, scalable, and clinically translatable solutions.

1. Introduction and Mechanisms of Nanotheranostics

Cancer remains a leading cause of global morbidity and mortality, emphasizing the necessity for innovative therapeutic approaches. Conventional modalities like chemotherapy, radiotherapy, and surgery are often hindered by non-specific toxicity, limited efficacy against aggressive tumors, and an inability to monitor therapeutic progress in real-time. Nanotheranostics, combining diagnostic and therapeutic functions into a single nanoscale platform, addresses these limitations by enabling real-time tumor imaging, precise drug delivery, and the continuous monitoring of treatment efficacy [1,2,3,4,5,6].
Among the techniques employed in nanotheranostics, photothermal therapy (PTT) and photodynamic therapy (PDT) stand out, due to their targeted mechanisms. PTT employs light energy to induce localized hyperthermia, causing tumor cell death with minimal impact on healthy tissues, while PDT uses photosensitizers activated by light to produce reactive oxygen species (ROS), thereby triggering oxidative stress and apoptosis in cancer cells. These methods offer spatiotemporal precision and reduced systemic toxicity compared to conventional therapies [1,2,3,4,7,8,9,10,11]. Beyond their direct cytotoxic effects, PTT and PDT have shown the potential to enhance tumor-specific immune responses, reducing the risk of recurrence and metastasis. For instance, nanoparticles combining photoreactive agents and immune modulators act as adjuvants, bolstering anticancer immunity by activating immune pathways within the tumor microenvironment [12].
Despite their promise, limitations such as poor light penetration, tumor hypoxia, and low specificity necessitate further innovation. Recent advances in nanotechnology have yielded solutions to these challenges. Multifunctional nanoplatforms, such as gadolinium-encapsulated graphene carbon nanoparticles (Gd@GCNs) and gadolinium-based polymer systems, enhance MRI-fluorescence imaging and relieve hypoxia to boost PDT efficacy [4,8,13]. Hybrid systems integrating PTT and PDT with complementary modalities, such as photoacoustic imaging (PAI) or immunotherapy, have shown synergistic effects. For instance, gold-based nanotheranostics couple imaging-guided PTT with an immune checkpoint blockade to enhance tumor-specific immunity [3,14,15]. Other platforms, like size-dynamic nanoparticles, enable precise drug release and rapid post-therapy clearance, thereby reducing systemic toxicity [5,16,17].
The utility of phototherapy extends beyond cancer treatment to addressing multidrug-resistant pathogens. Light-based therapies, including those employing conjugated polymers (CPs), offer an alternative to antibiotics by avoiding resistance development. These materials exhibit high absorption coefficients, photostability, and low cytotoxicity, making them effective in both photothermal and photodynamic applications for eliminating resistant microbes [18].
This paper explores the expanding field of PTT- and PDT-based nanotheranostics, emphasizing advancements in multimodal imaging, tumor-specific targeting, and therapeutic synergy. Emerging approaches, such as tumor microenvironment (TME)-responsive systems [13,19] and multifunctional nanoparticles for imaging-guided therapy [1,20,21], showcase the potential for next-generation, personalized cancer treatments.

2. Foundational Innovations in Nanosystem Mechanisms

The mechanisms underlying nanotheranostic systems provide the technological foundation for their utility in cancer diagnostics and therapy. These systems employ synergistic therapies, stimuli-responsive designs, multimodal imaging, and catalytic mechanisms to address the challenges posed by tumor microenvironments and therapeutic resistance.

2.1. Integrating Photothermal and Photodynamic Therapies

The combination of PTT and PDT has proven to be an effective approach in nanotheranostics. PVP-Cu-Sb-S nanoparticles [22] couple photothermal efficiency with ROS generation, enabling a tumor ablation mechanism under near-infrared (NIR) irradiation. Similarly, TT-DPP-based PDBr NPs [23] achieve imaging-guided therapy by combining high singlet oxygen quantum yields and photothermal effects.
Platforms like HAMnO2A nanotheranostics [24] amplify ROS production through CD44-mediated endocytosis and Mn2+/oxygen release, enhancing the targeted activity within the TME. Multimodal systems, such as MoWO NBs, integrate chemo, photothermal, and chemodynamic therapies (Chemo/PTT/CDT), providing treatment coupled with real-time biodistribution monitoring [25]. Additionally, APPG nanotheranostics [26] generate oxygen-independent free radicals, integrating triple-modal imaging with synergistic PDT/PTT to address hypoxic conditions in tumors.
Phototherapy has also emerged as a promising strategy against multidrug-resistant pathogens. Since the 1990s, light-mediated therapies have offered a reliable and efficient way to eliminate resistant microbes while avoiding the emergence of new resistance mechanisms [18]. Conjugated polymers (CPs), with their high absorption coefficients, photostability, low cytotoxicity, and processability, are effective photosensitizers and photothermal agents [18].

2.2. Stimuli-Responsive and Tumor Microenvironment Adaptation

Stimuli-responsive nanotheranostic designs enable dynamic adaptation to the tumor microenvironment. Size-changeable nanotheranostics [5] improve tumor retention and clearance by adjusting nanoparticle size, thereby reducing long-term toxicity. Similarly, PFTDPP nanotheranostics [2,27] use thermally initiated nitric oxide (NO) release mechanisms to provide spatiotemporal control of NO delivery, enabling dual NIR-II imaging and therapy for precise tumor ablation.
Acidic TME conditions are exploited by pH-sensitive platforms like hollow mesoporous organosilica nanocapsules [28] and PDA-modified nanoparticles (PHDP) [29], which facilitate controlled drug release in tumor-specific targeting. Redox-responsive systems, such as with AuNCs@SiO2 plasmonic nanotheranostics [30], utilize gold nanochain transformations in H2O2-rich environments to activate NIR-II photoacoustic imaging, enhancing diagnostic precision and therapeutic efficacy.
Recent advances in phototherapy have shown its ability to elicit tumor-specific immune responses. Nanoparticles, which are essential components of this approach, enable the simultaneous delivery of photo-reactive agents and immune modulators. Some nanoparticle-based systems function as adjuvants, enhancing anticancer immunity to combat tumor relapse and metastasis [12].

2.3. Multimodal Imaging for Enhanced Precision

Multimodal imaging technologies enhance tumor localization and treatment monitoring. Ag/Gd@BSA hybrid nanoparticles [31] integrate MR/CT/PA imaging with photothermal therapy, combining accurate diagnostics with effective tumor ablation. Gd-PEG-Bi nanoparticles [32] provide light-to-heat conversion efficiency for MRI, CT, and PAI-guided therapies, ensuring precise therapeutic outcomes.
Advanced systems like core/satellite nanotheranostics [33] combine photothermal ablation with radiotherapy, utilizing trimodal imaging to treat tumors without recurrence. Additionally, HSC-2 nanozymes [34] enhance NIR-II PA/FL imaging and enzyme-mediated ROS modulation, providing an effective tool for therapy and diagnosis.

2.4. Catalytic and Enzyme-Based Innovations

Catalytic and enzyme-mediated mechanisms play an important role in enhancing therapeutic efficacy. HSC-2 nanozymes [34] use enzymatic activity to modulate ROS production, improving photothermal effectiveness and tumor targeting. Similarly, PPy@BSA-MnO2 nanoprobes [35] combine chemodynamic therapy (CDT) with MRI-guided PTT, leveraging MnO2 nanozyme activity to disrupt redox homeostasis and enhance therapeutic efficacy.
These nanosystem mechanisms integrate synergistic therapies, stimulus responsiveness, multimodal imaging, and catalytic activity to address the complexities of cancer treatment. Platforms such as TT-DPP-based NPs [23], HAMnO2A nanotheranostics [24], and core/satellite systems [33] demonstrate the adaptability of these designs to dynamic tumor environments. Their additional potential for use in antimicrobial resistance and cancer immunotherapy highlights the broad utility of these technologies in advancing both cancer and infectious disease treatments [12,18].

3. Advances in Multifunctional Nanomaterials for Cancer Theranostics

Metal-based nanostructures, particularly those utilizing gold, have transformed photothermal therapy (PTT) for cancer treatment. Gold nanorods (GNRs) and gold-decorated silicon nanorods (Au@SiNRs) are widely recognized for their high photothermal conversion efficiency and stability, which are essential for sustained effectiveness during repeated laser treatments. These particles exhibit strong near-infrared (NIR) absorbance, enabling deep tissue penetration and the selective targeting of tumors. Advanced gold nanostructures, such as gold nanocages and gold–Prussian blue nanoparticle core–satellite structures, extend the potential of PTT by supporting multi-modal imaging, including MRI and CT, while also enabling radiosensitization to improve therapeutic specificity [3,9,14,36].
Gold’s versatility is further demonstrated by gold nanodandelions (GNDs), which exhibit pH-sensitive behavior in response to the acidic tumor microenvironment, enabling the selective activation of photothermal properties specifically within tumors, thereby enhancing treatment efficacy with minimized off-target effects. Magnetic nanoparticles, including iron oxide nanoparticles (IONPs) and manganese ferrite (MnFe2O4), are also instrumental in nanotheranostics for their dual imaging potential, particularly in enhancing MRI contrast, especially when combined with gadolinium or manganese. These nanoparticles support reactive oxygen species (ROS) generation under specific conditions, boosting the oxidative stress exerted on cancer cells to aid photodynamic therapy (PDT) effectiveness. Manganese oxide (Mn3O4) nanoparticles play a role in synergistic chemo-photothermal therapies, enhancing imaging contrast and ROS production for a more comprehensive approach to tumor targeting and ablation [5,11,20,37,38].
Hybrid nanoparticles, such as gold-coated iron oxide nanoparticles (Au@IONPs), offer enhanced MRI contrast and dual functionality, combining high-resolution imaging with potent photothermal properties, thus providing a holistic theranostic solution in cancer treatment [38]. Carbon-based nanostructures, such as gadolinium-encapsulated graphene carbon nanoparticles (Gd@GCNs), bring a combination of high relaxivity and fluorescence properties that are critical for precise imaging. Their inert carbon shell ensures biocompatibility and renal clearance, enhancing their safety and tolerability [8]. Additionally, single-walled carbon nanohorns (SWNHs) coated with hyaluronic acid enable the production of enzyme-responsive coatings that selectively release photosensitizers upon interaction with enzymes in the tumor microenvironment, optimizing their targeted therapeutic effects (Figure 1) [39].
Biocompatible coatings, such as polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP), contribute to the stability of photosensitive nanoparticles, facilitating extended circulation time and reduced systemic toxicity. PEG-coated nanoparticles functionalized with zinc phthalocyanine or PVP-coated antimony nanoparticles exhibit enhanced water solubility and photostability, which is essential for precision-guided therapies targeting deep-seated tumors [40,41].
Polymeric nanostructures are essential in photothermal therapy (PTT) and photodynamic therapy (PDT). Examples include semiconducting polymer nanoparticles and thermosensitive nitric oxide (NO) donors, which enable targeted therapeutic release upon NIR light exposure, enhancing treatment efficacy while protecting healthy tissues. Conjugated polymers paired with bovine serum albumin (BSA) for biomineralization further stabilize metal nanoparticles like gadolinium or iridium oxides, enhancing both MRI and CT imaging as well as photothermal conversion efficiency [1,2,42,43]. Polydopamine (PDA)-coated nanostructures, such as PDA-coated mesoporous silica nanoparticles, provide targeted and tumor-microenvironment-responsive drug release. These structures enable Fe3+ release, initiating chemodynamic therapy and amplifying ROS production, thereby reinforcing photothermal and oxidative stress-based treatments [44].
Silica-based nanoparticles and metal-organic frameworks (MOFs) also offer promising platforms for multi-modal imaging and targeted delivery. Mesoporous silica nanoparticles (MSNs), especially when combined with upconversion particles or gadolinium, enhance imaging modalities to support precise, image-guided therapy. Silica nanoshells and MOFs such as ZIF-8 facilitate the controlled release of encapsulated therapeutic agents in acidic tumor conditions, enhancing PA imaging and photothermal effects under targeted conditions [19,45,46,47]. Double-shell periodic mesoporous organosilica structures embedded with gold colloids provide robust stability and ultrasound imaging capability, supporting the use of guided PTT with minimal toxicity [48]. Zirconium-based MOFs (Zr-MOF@PPa/AF@PEG), incorporating photosensitizers and hypoxia-sensitive drugs, enable responsive drug release in hypoxic tumors, improving the efficacy of both PDT and chemotherapies [49].
Immune-targeting nanoparticles represent a significant advancement in selectivity and efficacy for PTT and PDT. Sialyl Lewis X-coated ultrasmall superparamagnetic iron oxide nanoparticles (USPIO-PEG-SLe(x)) enhance photothermal therapy while activating immune pathways, supporting tumor-specific targeting and complementing immune checkpoint therapies such as PD-L1 inhibition, thereby producing synergistic effects for improved therapeutic outcomes [15]. Aggregation-induced emission (AIE) fluorogens, when incorporated into nanoparticles, maintain high fluorescence without self-quenching, an advantage in NIR imaging that enables precise, real-time monitoring, which is crucial for imaging-guided PDT [50,51].
Transition metal oxides and quantum dots, including tungsten sulfide (WS2 QDs) and molybdenum disulfide/iron oxide (MoS2/Fe3O4) composites, enhance high-resolution imaging for integrated therapies. These materials facilitate CT, PA, and MRI imaging while boosting photothermal effects, providing valuable tools for addressing treatment-resistant tumors and deep-seated cancers. Their ROS generation capabilities and potential for radiosensitization make them highly effective in treating complex cancer types [52,53].
These advanced chemicals and materials have redefined PTT and PDT approaches in cancer treatment, providing multi-modal imaging capabilities, improved targeting precision, and enhanced therapeutic efficacy. From metal-based nanoparticles and silica frameworks to polymeric structures and immune-targeting agents, these materials demonstrate the progress achieved thus far in nanotheranostics. Despite the remaining challenges in terms of achieving deeper tissue penetration, controlled release mechanisms, and biocompatibility, these advancements mark substantial progress.
Table 1 explores a range of organic and inorganic materials tailored for imaging and therapeutic applications in cancer treatment. Organic materials, such as conjugated polymers, polypeptides, and glycol chitosan derivatives, focus on fluorescence and near-infrared (NIR) imaging while incorporating therapeutic functionalities like photothermal conversion, reactive oxygen species (ROS) production, and nitric oxide (NO) release. Examples include polypeptide-coated BODIPY micelles, which enable dual NIR-I/NIR-II imaging and ROS-driven tumor ablation, and protoporphyrin IX-conjugated glycol chitosan, which offers extended tumor retention and plasma membrane targeting for imaging-guided therapy. These systems demonstrate features like pH sensitivity, lysosome targeting, and controlled drug release, combining diagnostic and therapeutic capabilities with minimal toxicity and high efficacy.
Inorganic materials in the table include gadolinium oxide, gold nanostructures, and manganese ferrite nanoparticles, which are engineered for advanced imaging modalities such as MRI, photoacoustic (PA), and computed tomography (CT) imaging. These materials offer precise tumor targeting, high biocompatibility, and enhanced imaging resolution. Gold nanodandelions and silica-coated copper sulfide nanoparticles, for instance, activate in acidic tumor environments to enable synergistic imaging and photothermal therapy, while gadolinium-encapsulated graphene nanoparticles provide excellent MRI relaxivity and renal clearance. Structural innovations such as multi-branched designs and core-shell architectures amplify both imaging accuracy and therapeutic impact. Together, these organic and inorganic systems integrate diagnostic precision with therapeutic efficacy, representing a significant advancement in cancer diagnostics and therapy.

4. Nanomaterial Innovations for Enhanced PDT, PTT, and Combination Therapies

Photosensitizers play a critical role in enhancing the effectiveness of photodynamic therapy (PDT) for cancer treatment. Compounds like boron-dipyrromethene (BODIPY) are encapsulated within biocompatible carriers, providing stability and controlled activation in acidic lysosomal environments, which significantly boosts singlet oxygen production for targeted tumor ablation [10]. Indocyanine green (ICG) is another prominent photosensitizer, often being paired with mitochondria-targeted upconversion nanoparticles to penetrate deeper tissues, generating reactive oxygen species (ROS) upon NIR exposure, enabling the selective targeting of challenging tumor sites [60]. Additional photosensitizers, including pyropheophorbide-a (PPa) and chlorin e6 (Ce6), are embedded within metal–organic frameworks (MOFs) or other carriers for self-oxygenating PDT, which enhances both ROS yield and stability to effectively suppress tumors [49,61].
Nitric oxide (NO) donors, such as BNN6 and s-nitrosothiol (SNAP), release NO in response to heat generated from NIR laser irradiation, providing dual therapeutic support. This controlled release amplifies the effects of both photothermal and photodynamic therapies, enhancing tumor destruction while minimizing systemic toxicity [2,27]. Thermosensitive NO donors, when combined with polymers, create an environment conducive to immunogenic cell death, thereby enhancing the impact of therapy within the tumor microenvironment [42].
Incorporating immunotherapy agents with nanomaterials has shown remarkable potential for improving tumor targeting and destruction. For instance, PD-L1 aptamers (APDL1), when functionalized on gold nanorods, initiate immune checkpoint inhibition, enhancing the effects of photothermal therapy by engaging natural immune responses to target cancer cells [3]. CpG oligodeoxynucleotides (CpG ODNs), integrated with superparamagnetic iron oxide nanoparticles (SPIOs), stimulate immune responses and promote antigen release, which helps in suppressing primary tumors and metastasis, especially in conjunction with photothermal therapy (Figure 2) [62]. DNA aptamers such as AS1411 further augment immune responses by targeting cancer cell markers, creating synergy between photothermal therapy and immunotherapy [63].
Reactive oxygen species (ROS) generators are essential for maximizing the cytotoxic effects of PDT. Hematoporphyrin (HP), when encapsulated in mesoporous silica nanoparticles, produces ROS under NIR light, combining photothermal effects with ROS-induced cell damage to enhance cancer cell cytotoxicity [46]. Similarly, incorporating 6-amino flavone (AF) within Zr-MOFs releases ROS in hypoxic environments, enhancing photodynamic effects and supporting tumor cell destruction under oxygen-poor conditions [49]. Manganese dioxide (MnO2) also serves as both an oxygen generator and ROS catalyst, decomposing within the tumor microenvironment (TME) to release Mn2+ ions and ROS, thereby improving the efficacy of both photodynamic and chemodynamic therapies [24].
Chemotherapeutic agents like doxorubicin (DOX) are commonly utilized in PTT/PDT combinations to improve targeting and reduce side effects. DOX is often encapsulated within pH-sensitive or laser-triggered systems, such as Fe-LDH/DOX and polydopamine-Dox conjugates, enabling precise, stimuli-responsive drug release that synchronizes chemotherapy with photothermal therapy [21,36,64]. Other agents, including paclitaxel (PTX) and mitoxantrone (MTO), are embedded within nanoparticles to enable targeted chemotherapy and controlled release, improving therapeutic precision and minimizing toxicity [65,66].
Immune modulators, like decitabine, are incorporated within nanomicelles to activate antitumor immune responses and induce pyroptosis, an inflammatory cell death process beneficial in cancer treatment. By leveraging the STING pathway, decitabine enhances immune cell targeting and pathway activation [67]. Another immune enhancer, mitoxantrone (MA), when encapsulated in PcS-MA assemblies, interacts with nucleic acids to increase fluorescence and singlet oxygen production, amplifying immune responses through a combination of PDT and chemotherapy [68].
Combination therapies using dual-drug systems offer significant advantages for treating multidrug-resistant cancers. Polyprodrug nanoparticles (PDCN25-CDDP), for example, release paired chemotherapeutic agents under NIR irradiation, targeting cells that are resistant to single-drug regimens by combining chemotherapy with photothermal effects [69]. Formulations like ZnO2@Zr-Ce6/Pt, which integrate chemotherapeutic agents with photothermal properties and ROS generation, intensify cytotoxicity within resistant tumor microenvironments [70].
Targeting tumor-specific environments like hypoxia and high-GSH areas, hypoxia- and glutathione (GSH)-responsive agents such as Cy7-TCF and NLG919 are equipped with GSH-cleavable disulfide bonds that release therapeutic components under those conditions typical of tumors. This selective activation supports ROS production and immune responses, effectively targeting both primary and metastatic tumors [71]. Graphitic carbon nitride (g-C3N4@H1/H2) further serves as a platform for miRNA detection and photodynamic therapy, enabling real-time monitoring and targeted action at tumor sites [72].
Dual-modality photosensitizers that combine photothermal and photodynamic functions, such as when ICG is combined with methylene blue (ICG-MB), exhibit high photothermal conversion and ROS production, increasing phototoxicity and enabling effective cancer cell destruction through a combined approach [55]. IR780, when encapsulated in nanocarriers like GNP-Plu-IR780, also facilitates selective tumor targeting with high singlet oxygen yields under NIR exposure, improving PDT precision [73].
Radiosensitizers, including gold- and tungsten-based nanoparticles such as hyaluronic acid-modified gold nanocages (AuNCs-HA) and tungsten sulfide quantum dots (WS2 QDs), increase tumor sensitivity to radiation, enabling effective therapy at lower doses and minimizing harm to healthy tissues. Often combined with PTT, these agents provide both radiotherapy and photothermal effects, broadening options for tumor targeting [52,74].
Catalytic agents and oxygen-generating materials play vital roles in supporting chemodynamic therapy. For instance, encapsulating cuprous oxide (Cu2O) within ZnS/Cu2O@ZIF-8 enables the release of hydroxyl radicals in acidic environments, promoting ROS generation and offering imaging guidance for precise tumor targeting [19]. Oxygen-generating agents, such as nanoceria and PPy@BSA-MnO2, decompose in hypoxic tumor regions to supply essential oxygen, thereby enhancing both photodynamic and chemodynamic therapies, particularly within oxygen-deficient tumors [35,75].
Gene and miRNA modulators enable the targeting of specific genetic pathways in cancer. Drugs like HSP70-p53-GFP plasmid DNA, loaded within Prussian blue nanocubes, enable controlled gene expression and tumor cell ablation at specific temperatures, supporting gene therapy approaches for inducing apoptosis within cancer cells [76]. Similarly, miRNA carriers like graphitic carbon nitride (g-C3N4@H1/H2) facilitate real-time miRNA detection and photodynamic therapy, enabling precision treatment within complex tumor environments [72].
By integrating photosensitizers, immune modulators, chemotherapeutics, catalytic agents, and gene modulators within nanostructures, these strategies significantly improve targeting, ROS production, and therapeutic precision.
Table 2 summarizes the therapeutic applications of nanomaterials in PTT, PDT, chemotherapy, and immunotherapy. It showcases materials like gold nanorods and polydopamine nanoparticles, emphasizing combination therapies and stimuli-responsive systems. The entries emphasize the integration of multiple therapeutic modalities within a single platform, such as when combining PTT with PDT or chemotherapy for synergistic effects. Materials like gold nanorods and polydopamine-based systems highlight the versatility of these nanostructures for generating localized effects under light activation. A significant focus is placed on stimuli-responsive mechanisms, such as heat or pH triggers, enabling controlled drug release and minimizing side effects. Additionally, immunotherapeutic applications are increasingly combined with PTT, reflecting the growing interest in leveraging the body’s immune system to enhance tumor suppression.

5. Designing High-Efficiency, Responsive Nanotheranostics for Cancer Therapy

Achieving high photothermal conversion efficiency is essential for effective photothermal therapy (PTT), allowing nanomaterials to convert light into heat with minimal energy input. Materials such as gold nanorods (GNRs), Cu2-xS:Pt(0.3)/PVP, and Au@SiNRs are optimized for this purpose, generating substantial heat upon NIR exposure for ablating tumors without harming the surrounding healthy tissues. These materials demonstrate stability across repeated treatment cycles, as seen with gold-decorated silicon nanorods, making them ideal for use in long-term applications [6,9,38].
Controlled and targeted drug release within the tumor microenvironment (TME) enhances therapeutic accuracy, reducing off-target effects. Many nanostructures are designed with pH-sensitive or enzyme-responsive mechanisms that activate selectively within tumors. Gold nanodandelions, for instance, respond to matrix metalloproteinase activity in cancerous tissues, while polydopamine-Dox conjugates release their payload in the acidic conditions characteristic of the TME [10,21,37]. Materials such as melanin-coated magnetic nanoparticles and IR808-conjugated carbon nanohorns employ similar strategies, releasing therapeutic agents selectively within the TME [16,39].
Imaging compatibility is fundamental to nanotheranostic systems, enabling precise tumor localization and real-time monitoring. Nanoparticles with high relaxivity and fluorescence, such as gadolinium-based structures, facilitate MRI, CT, and FL imaging to support treatment planning and outcome tracking [4]. Other versatile materials, including copper sulfide on porphyrin-filled silica, Gd-upconversion nanoparticles (Gd-UCNPs) coated with a mesoporous silica shell (UCMSNs), and Ag2Se-based upconversion nanoparticles (UCNPs), further expand imaging capabilities by enabling PET, Cerenkov, and photoacoustic imaging for comprehensive tumor visualization [45,46,58]
Biocompatibility and efficient clearance are essential for clinical use, as they prevent potential long-term toxicity. Nanoparticles like gadolinium-encapsulated graphene carbon nanoparticles (Gd@GCNs) incorporate inert carbon shells that support renal clearance, enhancing patient safety [8].
Durability and reusability are also necessary to ensure sustainable nanotheranostic treatment. High-stability nanoparticles, like silicon nanorods with gold coatings and P@BDP polymer-based micelles, are crafted to maintain photothermal stability throughout multiple sessions, providing consistent results over time without compromising therapeutic efficiency [9,54].
Integrating immune activation capabilities into nanotheranostic systems offers added therapeutic benefits by leveraging the body’s natural defenses. Materials such as CpG oligodeoxynucleotide-functionalized SPIOs and USPIO-PEG-SLe(x) promote immune responses by encouraging T-cell infiltration and cytokine release, strengthening antitumor immunity and reducing recurrence risks [15,62]. By amplifying immune responses in combination with PTT and PDT, these materials enhance the treatment’s overall efficacy [42,67].
Environment-responsive activation for nanotheranostics enables selective therapeutic action within the TME. Nanoparticles that are responsive to specific conditions, such as acidity, hypoxia, or high GSH levels, enhance treatment precision. Mn-doped calcium phosphate nanoparticles and GSH-responsive prodrugs (Cy7-TCF-SS-NLG) can be engineered to activate within acidic or GSH-rich environments, limiting off-target effects [71,80]. Figure 3 shows Cy7-TCF-SS-NLG PNAs developed for combined photothermal therapy and immunotherapy, wherein GSH triggers Cy7-TCF-OH release, enhancing tumor ablation, ROS generation, and immune activation to boost antitumor immunity and prevent metastasis [71].
Multi-modal imaging is vital for effective treatment guidance, providing real-time monitoring and precise localization. Nanoparticles like PFTQ-PEG-Gd and Gd-PEG-Bi NPs support MRI, CT, and photoacoustic imaging, enabling comprehensive tumor tracking and dose distribution [32,77]. Dual-modal platforms, such as EuB6@RGD-K and the PDT-based nanotheranostics, Pa-Mn&CH-A@P and MMCC@EM, further enhance the spatial accuracy of MRI and fluorescence imaging [17,81,82].
High photostability and deep tissue penetration are necessary for treating difficult-to-access tumors. NIR-II-absorbing materials, including IT-S and NIR-II nanotheranostics, deliver superior tissue penetration and contrast, facilitating accurate imaging and the treatment of deep-seated tumors [83,84]. Photostable agents like AuNCs-HA and PDBr enable stable heat generation with minimal dark toxicity, directing tumor ablation while sparing the adjacent healthy tissue [23,74].
ROS production and oxygenation are crucial in hypoxic tumor environments to support PDT. MnO2-based particles (HAMnO2A) generate both oxygen and ROS under acidic conditions, enhancing PDT efficacy and enabling chemodynamic therapy by counteracting hypoxia [24].
Precise control over drug release within the TME ensures therapeutic efficacy while protecting healthy tissues. Environment-responsive systems like ZnO2@Zr-Ce6/Pt, which releases agents in acidic tumor conditions, and GSH-sensitive DPP derivatives offer selective activation, confining the cytotoxic effects to tumor sites [70,85]. Platforms like PDA@HMONs-DOX/PFP and Ho-MPDA with cell membrane coatings also facilitate pH and GSH-responsive release, ensuring localized delivery and minimizing systemic exposure [29,65].
These attributes underscore the intricate design requirements for effective PTT and PDT in nanotheranostics. Key properties such as high photothermal efficiency, controlled release, multi-modal imaging compatibility, and immune activation enhance therapeutic precision, patient safety, and treatment outcomes.
Table 3 presents the stimuli-responsive and targeting mechanisms of nanomaterials, detailing their activation triggers, like pH, enzymes, or light, as well as their tumor-specific targeting strategies. Most materials utilize tumor-specific triggers like low pH, hypoxia, or enzymatic activity to achieve targeted activation. This reflects a growing emphasis on minimizing systemic toxicity by confining therapeutic effects to the tumor microenvironment. Dual or multi-stimulus responsiveness (e.g., pH and redox sensitivity) is frequently reported, showcasing the effort to overcome tumor heterogeneity. Active targeting, such as using peptides or ligands like hyaluronic acid, is a common strategy to enhance tumor specificity. Overall, the trend is toward highly selective and adaptive systems to improve therapeutic precision.
Table 4 highlights the physicochemical properties of the nanomaterials used in nanotheranostics, such as relaxivity, photothermal efficiency, and singlet oxygen quantum yields, which are critical for their imaging and therapeutic roles. Materials are consistently engineered for high photothermal efficiency and relaxivity, to enhance imaging and therapy. Dual functionalities, such as combining oxygen generation with heat production, are common, underscoring efforts to address hypoxia in tumors. Properties like high singlet oxygen yields and excellent photostability are optimized to improve therapeutic outcomes while ensuring durability under physiological conditions. Many entries highlight those materials that balance efficiency with biocompatibility, reflecting the clinical need for safe, effective, and multifunctional platforms. These properties demonstrate the interplay between design precision and therapeutic functionality.

6. Key Preparation and Processing Techniques for Effective Nanotheranostic Cancer Treatments

Biomineralization and self-assembly techniques are fundamental in nanotheranostics manufacturing, offering precise control over nanoparticle size and composition. For instance, bovine serum albumin (BSA) serves as a biomineralization template for synthesizing uniform gadolinium and iridium oxide nanoparticles, resulting in biocompatible structures suitable for MR/CT imaging in cancer treatment [1]. Similarly, self-assembly is used to construct nanoparticles like Gd-TCPP, which encapsulate gadolinium porphyrin complexes through non-covalent interactions, enhancing both dual-modal imaging and photodynamic therapy efficacy [4].
Surface functionalization is crucial for enhancing specificity and biocompatibility in nanotheranostics. Gold nanorods, for example, are modified with PD-L1 aptamers, directing the particles to tumor sites and improving immune-targeted responses and photoacoustic imaging [3]. Additionally, coatings like PEGylation, folic acid, and chitosan improve nanoparticle stability and reduce immunogenicity. For instance, Mn3O4 nanoparticles coated with polydopamine, folic acid, and PEG ensure targeted delivery, with minimal side effects and prolonged circulation in vivo [20].
Core-shell and core-satellite structures enhance multi-modal imaging and therapy within a single nanoparticle. Prussian Blue-AuNP core-satellite nanoparticles (CSNPs) integrate MR-CT imaging with photothermal and radiotherapy (PTT-RT) capabilities, improving cancer treatment outcomes [14]. Likewise, gadolinium-doped upconversion nanoparticles (UCNPs), when combined with mesoporous silica, facilitate multi-functional platforms that deliver combined chemo-, radio-, and photodynamic therapies within one session [46].
Environment-responsive carriers in nanotheranostics enable selective drug release within the tumor microenvironment (TME). Polydopamine-doxorubicin conjugates and polyprodrug nanoparticles release drugs in response to acidic pH or NIR light, ensuring that therapeutic agents are activated specifically within the TME [21,69]. Metal–organic frameworks (MOFs) like ZIF-8 also decompose under acidic conditions, delivering their payload within the cancer cells to enhance their chemodynamic and photothermal effects [19].
Near-infrared (NIR) activation provides precise control over therapeutic interventions. Systems like Cu2₋ₓS and UCNPs@CS@Ag2Se use NIR light to trigger therapeutic reactions such as platinum ion release, enabling targeted and controlled cancer treatment [6,58]. Additionally, iRGD-coated gold nanocages and semiconducting polymer nanoparticles (PFTDPP-SNAP) combine NIR-triggered heat release with photothermal and immunotherapeutic effects, increasing treatment specificity and reducing adverse effects [27,86].
Encapsulation enhances drug stability and target specificity, ensuring effective delivery to tumor sites. Liposomal encapsulation of IR-780 nanoparticles, for example, increases photostability and solubility, which are essential for targeted cancer therapy [90]. Biocompatible coatings, such as erythrocyte membranes and BSA, further prolong the circulation time and optimize immune evasion, as seen with MMCC@EM and Ag/Gd@BSA nanoparticles [17,31].
Enzyme-responsive and magnetically targeted systems enable highly localized therapy. Single-walled carbon nanohorns (SWNHs) conjugated with hyaluronic acid disassemble in response to tumor-associated enzymes, confining drug release to the TME [39]. Similarly, melanin-coated nanoparticles functionalized with RGD peptides enable magnetic targeting for precise tumor localization and controlled release [16].
Redox-sensitive and pH-responsive bonding in nanostructures facilitates controlled drug release by adapting to the unique chemical conditions within tumors. Glutathione-sensitive prodrugs (Cy7-TCF-SS-NLG) disassemble in the high-GSH environment of tumor cells, while MnO2-based particles (HAMnO2A) generate ROS and release oxygen in response to the acidic TME, enhancing PDT in hypoxic conditions [24,71].
To achieve high fluorescence stability and prevent quenching, some systems use aggregation-induced emission (AIE) properties. Nanoparticles like BSA-PhENH2-Bi2S3 maintain stable fluorescence under biological conditions, thereby supporting consistent imaging-guided therapy [50]. This property is especially valuable for real-time monitoring, providing stable imaging contrast during treatment.
Multi-modal platforms integrate functionalities within single structures, improving imaging and treatment accuracy. For example, APPG nanoparticles with polydopamine coatings, gadolinium, and PdAu alloys enable MRI, CT, and photoacoustic imaging, supporting precise therapeutic guidance within hypoxic tumors [26]. Core-shell architectures like UCNPs-SiO2 and Au@MnO2@PM provide tumor targeting and synergistic PTT/PDT, facilitating comprehensive treatment approaches [91,92].
Biomimetic coatings enhance biocompatibility and immune evasion, increasing nanotheranostic effectiveness in vivo. BSA-templated Gd@BSA and 4T1 cell membrane-coated Ho-MPDA nanoparticles, for instance, provide natural camouflage, thereby prolonging circulation time and enabling efficient tumor targeting [65,78] These coatings minimize immune detection and aid concentration of the therapeutic agents at the target site, with minimal off-target effects.
In situ synthesis techniques allow therapeutic agents to be produced directly within tumors, maximizing their effectiveness while minimizing systemic exposure. Ingenious cross-linked nanogel (DSA) nanogels, for example, generate active drugs like protoporphyrin IX in tumor cells, enhancing ROS production and PDT efficiency [93].
The preparation and processing of nanotheranostic agents for photothermal and photodynamic therapies require advanced techniques that are tailored for targeted delivery, stability, and biocompatibility. Methods such as biomineralization, functionalization, core-shell structuring, NIR activation, and environment-responsive release mechanisms have enabled the development of sophisticated nanotheranostics that combine multi-modal imaging with precise therapy.

7. Evaluating Nanotheranostics for Precision Imaging and Responsive Cancer Therapy

Nanotheranostics are rigorously evaluated for their multi-modal imaging capabilities, which are essential for precise tumor localization and real-time therapy guidance. Imaging techniques like MRI, CT, fluorescence (FL), and photoacoustic (PA) imaging are employed to visualize tumors, monitor biodistribution, and validate therapeutic outcomes, with advanced modes such as dual T1/T2 MRI, NIR-II, and multispectral optoacoustic tomography (MSOT) used for enhancing tumor mapping and treatment precision [1,4,5,19,31,77,82,83]. These imaging assessments can confirm selective tumor accumulation, minimizing off-target localization and supporting therapeutic specificity through techniques like PA imaging, fluorescence tracking, and magnetic targeting. Additionally, some nanotheranostics are engineered to activate selectively within the tumor microenvironment (TME), responding to conditions like acidity or specific enzymes to boost targeting accuracy [8,10,11,49,80,82].
Photothermal conversion efficiency and stability under NIR irradiation are crucial for effective tumor ablation in PTT; tests are used to measure conversion rates and thermal stability to ensure consistent heat generation in tumor tissues. Stability assessments during thermal cycling and photobleaching resistance further confirm their reliability in the TME [2,7,9,21,40,55,84,90]. Temperature control tests focus on precision heat delivery, ensuring tumor cell ablation without affecting the surrounding healthy tissues. Evaluations also confirm pH- and redox-responsive activation within the TME, enabling controlled thermal responses [27,44,48,54,71].
In PDT, reactive oxygen species (ROS) generation is essential for targeted cancer cell cytotoxicity; tests examine ROS production under various TME conditions, such as hypoxia or pH sensitivity, to ensure sustained oxidative stress within tumors but with minimal systemic impact. Stimuli-responsive mechanisms, such as GSH activation, are used to confirm targeted cytotoxic effects [10,19,25,41,80,94]. Some nanotheranostics are designed to mitigate hypoxia within the TME, improving PDT efficacy and stimulating immune responses like T-cell infiltration and MHC activation for enhanced antitumor immunity [17,86,95].
The efficacy of dual or multi-modal treatments that combine PTT, PDT, and chemotherapy is assessed to verify therapeutic synergy. These tests measure tumor inhibition rates, ROS production under dual stimuli, and the therapeutic index, confirming the enhanced efficacy of combined approaches in treating both primary and metastatic tumors [16,20,29,46,76,96]. For platforms integrating chemodynamic therapy (CDT) with PTT, past evaluations focus on hydroxyl radical production and immunogenic cell death (ICD) induction, thereby promoting apoptosis and enhancing immune engagement for comprehensive cancer treatment [25,35,71].
TME-responsive drug release is essential for targeting specificity, with pH, redox, or enzyme triggers that allow selective activation within the TME. Tests for pH/light-triggered and GSH-responsive release confirm precise delivery and activation within acidic or hypoxic tumor regions, enhancing therapeutic selectivity [5,28,71,97]. Hypoxia modulation tests assess oxygen-generating capabilities to address hypoxic limitations in ROS production, along with evaluations monitoring TAM (tumor-associated macrophages) reprogramming and hypoxia relief, which bolster PDT, CDT, and immunotherapy efficacy [17,44,70].
Selective cellular uptake and cytotoxicity toward cancer cells are tested using cytotoxicity assays like the MTT test to gauge cell viability post-treatment, while cellular uptake studies ensure efficient therapeutic payload delivery within tumors. Additional assays track apoptosis and necroptosis pathways, providing insights into nanotheranostic-induced cell death and confirming that there was minimal impact on healthy tissues [22,60,98,99]. Biocompatibility and in vivo safety evaluations measure systemic clearance and organ accumulation, confirming nanotheranostics’ safety for long-term application [9,58,61,100].
Immune modulation tests assess immune system activation, which is vital for therapeutic efficacy. Cytokine release, T-cell infiltration, and pathways like PD-L1 engagement are monitored to confirm nanotheranostics’ potential to stimulate the immune response, enhancing cancer cell elimination and potentially reducing recurrence risk [42,62,63,67,95]. Genetic activation assessments, such as RNA sequencing and MMP activity analysis, track genetic responses and pathway activation, including HIF-1α expression and necroptosis/apoptosis pathways, to verify their precise therapeutic targeting under PTT or PDT [15,76,86].
System stability and photostability are tested to ensure consistent functionality under diverse pH conditions and with laser irradiation. Photostability evaluations confirm steady therapeutic performance, while structural characterizations measure MRI/CT contrast and thermal stability, ensuring compatibility with imaging and therapeutic requirements [31,41,84,94]. Simplified synthesis methods, such as one-pot protocols, also verify that nanotheranostics retain their stability and biocompatibility, supporting scalability in production [29,50,84].
Real-time tumor tracking and biomarker detection tests support in situ intervention. Dual-mode imaging, such as FL/MR or PA/MR, enables real-time chemiluminescence feedback, which is crucial for responsive TMEs. Biomarker detection, like miRNA imaging, is validated to ensure precise targeting and therapeutic action within live cells [49,51,82,89]. Gene expression monitoring of oncogenic markers like miRNA confirms the nanotheranostic’s effectiveness in addressing tumor heterogeneity, supporting real-time tracking and precision therapy [51,72].

8. Multifunctional Nanotheranostics: Advancing Precision Cancer Therapy and Monitoring

The development of multifunctional nanotheranostic platforms has significantly advanced tumor targeting and monitoring by integrating advanced imaging techniques such as MRI, CT, photoacoustics, and fluorescence imaging. This combination enables precise tumor localization and real-time therapeutic monitoring, enhancing treatment accuracy and minimizing off-target effects, which are crucial for improving patient outcomes. Studies confirm that nanoparticles engineered for dual or trimodal imaging enhance tumor tracking and targeting, thereby optimizing treatment delivery for more personalized approaches [1,8,9,31,32,36,43,46,47,48,52,62,65,77,81,88,101,102].
Combining photothermal therapy (PTT) with photodynamic therapy (PDT), chemotherapy, or immunotherapy has proven effective in amplifying therapeutic effects and reducing tumor recurrence. Such platforms often leverage tumor-specific conditions like NO release, pH, or redox sensitivity to achieve controlled drug release, which increases therapeutic precision while reducing systemic toxicity. Platforms that release agents in response to these conditions demonstrate significant tumor reduction, enhancing the potential for tumor ablation with lower overall dosages [2,10,13,52,62,63,64,67,74].
The use of stimuli-responsive materials enables selective drug release and therapeutic activation within the tumor microenvironment (TME). These nanotheranostics respond to environmental cues such as pH, redox states, or specific enzymes, enabling localized treatment with minimized off-target effects. Dual pH- and redox-sensitive agents are particularly effective, releasing therapeutic drugs directly at the tumor site, optimizing both efficacy and safety [13,28,64,71,102,103,104].
Integrating PTT or PDT with immunotherapy has shown potential, not only for tumor ablation but also for activating the immune response, which is crucial in preventing metastasis and recurrence. By incorporating immune checkpoint inhibitors with PTT, these platforms stimulate immune cell infiltration within tumors, promoting a systemic anti-tumor response. This integration of immune activation with traditional therapy has demonstrated promising results in tumor suppression and the immune response [15,42,62,63].
Hypoxia and other TME conditions often hinder conventional therapies, prompting the development of nanotheranostics that can modulate these factors by generating oxygen or reactive oxygen species (ROS) to counteract hypoxia. This approach enhances PDT effectiveness in hypoxic tumors, reducing systemic side effects and boosting therapeutic efficiency, particularly with platforms that respond to hypoxic conditions to stimulate ROS generation [17,70,95,105].
Innovative delivery techniques, like convection-enhanced delivery (CED), are employed to enhance the retention and penetration of nanotheranostics in challenging tumors, including brain tumors. By enabling better accumulation and retention at the tumor site, CED significantly enhances treatment efficacy in hard-to-reach or dense tumors, where conventional delivery methods fall short [90].
Ensuring biocompatibility is essential for the clinical translation of nanotheranostic platforms. Biocompatible materials like albumin, PEG, and polydopamine have been extensively studied as they promote biodegradability and minimize toxicity, enabling effective tumor ablation with reduced systemic effects. Materials such as human serum albumin and FDA-approved polymers are frequently incorporated to enhance clinical safety profiles [6,8,20,29,32,40,50,51,55,56,57,58,76,78,86,106]. Combining PTT, PDT, and chemodynamic therapy (CDT) with chemotherapy presents a powerful approach, achieving higher tumor inhibition rates and lowering recurrence. Multi-therapy nanotheranostics that integrate chemo-photothermal effects or chemodynamic responses leverage multiple tumoricidal mechanisms, which proves particularly effective for overcoming chemoresistance and delivering complementary effects for potent tumor eradication [36,49,52,74,94].
Materials with high photothermal conversion efficiency, such as polypyrrole and plasmonic gold nanocomposites, provide effective tumor ablation at a lower laser power, minimizing the collateral damage to surrounding tissues. These platforms are particularly beneficial in cases where precision in localized tumor ablation is essential as they ensure safety and accuracy, even at reduced power settings [30,35].
Beyond cancer, nanotheranostic platforms have also shown potential in treating bacterial infections and drug-resistant pathogens. By leveraging photodynamic and photothermal effects, these systems selectively target and destroy microbial cells, expanding nanotheranostics into new therapeutic areas such as antimicrobial treatment [107].
The integration of imaging into nanotheranostic platforms not only enhances their accuracy in targeting but also allows real-time monitoring for adaptive therapy. This capability facilitates personalized treatment adjustments based on immediate feedback, maximizing treatment efficacy while minimizing side effects through dynamic therapy modification [32,65,76,86,102].
To address concerns over long-term toxicity, biodegradable materials like polydopamine and human serum albumin are increasingly used to enhance clearance and reduce the risk of nanoparticle accumulation. Such materials offer a safe, sustainable approach, which is essential for nanotheranostics in clinical applications [29,57,78,106].
Certain nanotheranostic platforms are engineered to induce immunogenic cell death, which activates the immune system to prevent tumor recurrence and metastasis. This approach is particularly effective in immunologically challenging cancers, as it creates immune memory against the tumor, providing a durable response with sustained tumor suppression [95].
Table 5 details the therapeutic outcomes and effectiveness of various nanomaterials, focusing on tumor suppression, immune activation, and enhanced imaging guidance in PTT, PDT, and combination therapies. The table reveals a clear emphasis on combining therapies (e.g., PTT and PDT) for enhanced tumor suppression. Immune activation through nanomaterial-mediated checkpoint inhibition or immune cell infiltration is a recurring theme, indicating a shift toward immunotherapy integration. Imaging guidance is a consistent feature since it enables real-time monitoring and dose optimization for better outcomes. Synergistic effects, such as ROS generation alongside thermal ablation, are leveraged to achieve complete tumor suppression with minimal toxicity. Overall, the materials demonstrate significant advancements in maximizing therapeutic efficacy through multi-pronged approaches.

9. Overcoming Barriers in Nanotheranostic Cancer Therapies for Clinical Integration

The transition of nanotheranostics from research innovation to clinical application requires overcoming challenges such as synthesis complexity, tissue penetration, biocompatibility, stability, and safety. Advances in nanosystem mechanisms and personalized therapies provide potential solutions, but addressing these factors is critical for successful clinical translation.
  • Balancing Synthesis Complexity with Clinical Feasibility
Achieving a balance between synthesis complexity and scalability is essential for clinical implementation. Complex platforms such as BSA@Gd2O3/IrO2 nanoparticles (BSA@Gd2O3/IrO2 NPs) [1] and AuPd-cluster nanotheranostics (AuPd-BSA CN) [89] demonstrate advanced multi-metallic designs and dual-modal imaging capabilities, enhancing therapeutic performance. However, these systems require sophisticated manufacturing techniques that may hinder scalability.
Simplified designs such as PEG-coated biodegradable polymer nanotheranostics [41] offer an alternative option, maintaining efficacy while reducing synthetic demands, thereby making large-scale production feasible. Moderately complex systems, including ZnS/Cu2O@ZIF-8@PVP nanotheranostics [19] and dual-stimuli-responsive nanotheranostics (RMDI) [16], integrate tumor-specific or external stimuli responses to optimize drug delivery. These systems strike a balance between innovation and practicality, enhancing their potential for clinical translation.
  • Tumor Heterogeneity and Immune Risks
Tumor heterogeneity and immune evasion present significant barriers to consistent therapeutic outcomes. Stimuli-responsive platforms, such as Zr-MOF@PPa/AF@PEG nanocomposites [49], activate hypoxia-sensitive drugs, targeting acidic and oxygen-deprived tumor regions. Redox-activatable NIR-II nanotheranostics [83] adapt to variable redox and acidic conditions, improving targeted imaging and therapy. Polypyrrole-based nanotheranostics (DOX@HA-PPys) [97] integrate chemo/photothermal dual therapy with stimuli-responsive drug release, addressing therapy-resistant tumor subpopulations.
To counter immune suppression and evasion, platforms like CsBPNs [103] combine hypoxia imaging with photothermal therapy and immunotherapy, enhancing immune activation. USPIO-PEG-SLe(x) nanoparticles [15] enhance anti-PD-L1 immunotherapy, improving T-cell infiltration and cytokine release. For glioblastoma, neutrophil-targeting semiconducting polymer nanotheranostics (SSPN(iNO)) [42] integrate NIR-II fluorescence imaging, photothermal therapy, and nitric oxide immunotherapy to reverse immune suppression and achieve tumor-specific targeting.
  • Enhancing Tissue Penetration for Effective Therapy
Deep tissue penetration is critical for treating solid and deep-seated tumors. DOX/ZnO2@Zr-Ce6/Pt/PEG nanotheranostics [70] generate endogenous oxygen within the tumor microenvironment, alleviating hypoxia and enhancing photodynamic and chemo-photothermal therapies. Similarly, CsBPNs [103] integrate hypoxia imaging and photothermal therapy to enhance penetration and improve therapeutic outcomes in hypoxic regions.
Advanced imaging systems support both diagnostics and targeted delivery for deep-seated tumors. Ultrasmall Ag2Se-decorated UCNPs [58] provide tetra-modal imaging (CT, PA, UCL, and DSL) and photothermal therapy, enabling precise localization and treatment. Gadolinium-chelated polymer nanoparticles (PFTQ-PEG-Gd NPs) [77] integrate MRI and NIR-II imaging for guided therapies, achieving high-resolution diagnostics and targeted treatment.
Near-infrared (NIR-II) technology enhances penetration and precision. Redox-activatable nanotheranostics [83] respond to tumor-specific conditions for precise localization, while hyaluronic acid-functionalized FeWO4 nanoparticles (HA-FeWO4) [108] combine multimodal imaging with photothermal therapy to target tumor cells specifically, minimizing any collateral damage.
  • Optimizing Tumor Microenvironment Responsiveness
TME-specific designs enable nanotheranostic platforms to target and adapt to the unique challenges of the tumor microenvironment. Thermosensitive PMFLB nanotheranostics [44] utilize heat-responsive mechanisms to enhance hyperthermia and chemodynamic therapy, triggering the release of Fe3+ to generate hydroxyl radicals. Similarly, MONs@PDA-ICG nanotheranostics [79] generate oxygen and Mn2+ ions for MRI imaging, addressing hypoxic regions effectively. Zr-MOF@PPa/AF@PEG nanocomposites [49] activate hypoxia-sensitive drugs through oxygen consumption, improving precision in acidic and oxygen-deprived conditions.
Oxygen self-supply systems such as PMOF@AuNP/hairpin nanotheranostics [109] integrate oxygen generation and miRNA detection, alleviating hypoxia and enhancing tissue penetration. These capabilities improve their adaptability across diverse cancer types and clinical scenarios.
  • Biocompatibility, Stability, and Safety
Biocompatibility and stability are fundamental for ensuring long-term safety and effectiveness. Platforms like gadolinium-porphyrin-based polymer nanoparticles (Gd-PNPs) [4] and gold-decorated silicon nanorods (Au@SiNRs) [9] combine high stability with compatibility, reducing adverse interactions with healthy tissues.
Innovations such as vehicle-free ICG-MB nanotheranostics [55], utilizing FDA-approved dyes, enhance photostability and minimize systemic toxicity. Liposomal IR-780 nanotheranostics (ILs) [90] improve tumor-specific delivery and photostability through liposomal encapsulation, offering targeted therapies for sensitive regions like the brain.
To minimize toxicity, platforms like Zn2+-doped Prussian Blue nanotheranostics (SPBZn(10%)) [99] and BSA-PhENH2-Bi2S3 nanoparticles [50] focus on precise tumor targeting and minimal off-target effects. These systems balance efficacy and safety, which is crucial for clinical translation.
  • Overcoming Resistance and Precision Challenges
Therapeutic resistance and precision targeting remain challenges in cancer treatment. Polypyrrole-based nanotheranostics (DOX@HA-PPys) [97] use stimuli-responsive drug release for targeting resistant tumor subpopulations, combining chemo/photothermal dual therapy with imaging. Holmium (III)-doped nanospheres [65] enable MRI-guided chemo-photothermal therapy, providing effective drug delivery and precise targeting in complex tumor microenvironments.
For glioblastomas, europium hexaboride nanotheranostics (EuB6@RGD-K) [81] integrate MRI-guided photodynamic therapy and tumor-specific targeting to overcome treatment barriers, improving outcomes for these resistant brain tumors.
  • Integrating Multimodal Imaging and Personalized Therapies
Multimodal imaging technologies improve diagnostic precision and real-time treatment monitoring. NIR-II imaging-guided nanotheranostics (P@BDP) [54] combine photodynamic and photothermal therapies with high-resolution imaging, while dual-modal MRI/chemiluminescence nanotheranostics (Pa-Mn&CH-A@P) [82] integrate MRI with ROS-sensitive chemiluminescence feedback for evaluating therapeutic efficacy.
Platforms like GCGLS nanoparticles [110] and hyaluronic acid-modified gold nanocages (AuNCs-HA) [74] seamlessly integrate imaging and therapy, ensuring precise tumor localization and effective ablation. Hybrid nanotheranostics [45] and albumin-based “nanoglue” nanotheranostics (HSA-PTX-DVDMS) [66] exemplify personalized therapies with high specificity and adaptability.
Addressing clinical challenges requires platforms like PB@Au core-satellite nanoparticles [14], MONs@PDA-ICG nanotheranostics [79], and GCGLS nanoparticles [110] to integrate precision targeting, stimulus responsiveness, and multimodal imaging. These systems offer adaptable and effective solutions for advanced cancer treatment.
Table 6 outlines the biocompatibility, toxicity, and clearance profiles of nanomaterials, focusing on properties like renal clearance, minimal systemic toxicity, and in vivo safety. The entries consistently prioritize biocompatibility and effective clearance, using materials designed to minimize systemic toxicity and ensure safe elimination. Biodegradable systems and renal clearance mechanisms are common features, reflecting a strong focus on patient safety. Tumor-specific activation further enhances selectivity, reducing off-target effects. Gold and Gd-based systems are highlighted for their promising balance of effectiveness and safety. The emphasis on long-term biocompatibility indicates a forward-thinking approach to meet the regulatory requirements for clinical applications. There is a clear shift toward materials that combine high efficacy with minimal long-term risks.

10. Conclusions

Photothermal and photodynamic nanotheranostic platforms represent a transformative approach to precision oncology, offering enhanced therapeutic efficacy through targeted delivery and real-time imaging. While challenges persist regarding synthesis scalability, deep tissue penetration, and long-term biocompatibility, innovative strategies are being developed to overcome these obstacles. Future research emphasizes simplified synthesis methods, multi-stimulus responsiveness, and controlled immune activation to optimize these platforms for clinical application. The ongoing advancements in nanotheranostics are poised to revolutionize cancer treatment by enabling personalized therapies that are both effective and minimally invasive, ultimately improving patient outcomes and quality of life.

Author Contributions

The authors confirm contributions to the paper as follows: conceptualization, writing, review, and editing, H.O.; investigation, review, and editing, S.D.C. All authors have read and agreed to the published version of the manuscript.

Funding

This review article received no external funding.

Acknowledgments

The authors partly used the OpenAI Large-Scale Language Model to maximize accuracy, clarity, and organization. The authors have reviewed and edited the output and take full responsibility for the content of this publication.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Cai, C.; Tian, F.; Ma, J.; Yu, Z.; Yang, M.; Yi, C. BSA-templated synthesis of Ir/Gd bimetallic oxide nanotheranostics for MR/CT imaging-guided photothermal and photodynamic synergistic therapy. Nanoscale 2023, 15, 4457–4468. [Google Scholar] [CrossRef] [PubMed]
  2. Chang, K.; Sun, X.; Qi, Q.; Fu, M.; Han, B.; Zhang, Y.; Zhao, W.; Ni, T.; Li, Q.; Yang, Z.; et al. NIR-II Absorbing Conjugated Polymer Nanotheranostics for Thermal Initiated NO Enhanced Photothermal Therapy. Biosensors 2023, 13, 642. [Google Scholar] [CrossRef]
  3. Chang, R.; Li, T.; Fu, Y.; Chen, Z.; He, Y.; Sun, X.; Deng, Y.; Zhong, Y.; Xie, Z.; Yang, Y.; et al. A PD-L1 targeting nanotheranostic for effective photoacoustic imaging guided photothermal-immunotherapy of tumor. J. Mater. Chem. B 2023, 11, 8492–8505. [Google Scholar] [CrossRef] [PubMed]
  4. Chen, W.; Zhao, J.; Hou, M.; Yang, M.; Yi, C. Gadolinium–porphyrin based polymer nanotheranostics for fluorescence/magnetic resonance imaging guided photodynamic therapy. Nanoscale 2021, 13, 16197–16206. [Google Scholar] [CrossRef] [PubMed]
  5. Cheng, G.; Zong, W.; Guo, H.; Li, F.; Zhang, X.; Yu, P.; Ren, F.; Zhang, X.; Shi, X.; Gao, F.; et al. Programmed Size-Changeable Nanotheranostic Agents for Enhanced Imaging-Guided Chemo/Photodynamic Combination Therapy and Fast Elimination. Adv. Mater. 2021, 33, 2100398. [Google Scholar] [CrossRef] [PubMed]
  6. Dong, L.; Zhang, P.; Xu, X.; Lei, P.; Du, K.; Zhang, M.; Wang, D.; Feng, J.; Li, W.; Zhang, H. Simple construction of Cu2−xS:Pt nanoparticles as nanotheranostic agent for imaging-guided chemo-photothermal synergistic therapy of cancer. Nanoscale 2018, 10, 10945–10951. [Google Scholar] [CrossRef]
  7. Chen, C.H.; Wu, Y.-J.; Chen, J.-J. Gold Nanotheranostics: Photothermal Therapy and Imaging of Mucin 7 Conjugated Antibody Nanoparticles for Urothelial Cancer. BioMed Res. Int. 2015, 2015, 813632. [Google Scholar] [CrossRef]
  8. Chen, H.; Qiu, Y.; Ding, D.; Lin, H.; Sun, W.; Wang, G.D.; Huang, W.; Zhang, W.; Lee, D.; Liu, G.; et al. Gadolinium-Encapsulated Graphene Carbon Nanotheranostics for Imaging-Guided Photodynamic Therapy. Adv. Mater. 2018, 30, e1802748. [Google Scholar] [CrossRef]
  9. Cui, M.; Liu, S.; Song, B.; Guo, D.; Wang, J.; Hu, G.; Su, Y.; He, Y.; Cui, M.; Liu, S.; et al. Fluorescent Silicon Nanorods-Based Nanotheranostic Agents for Multimodal Imaging-Guided Photothermal Therapy. Nano-Micro Lett. 2019, 11, 73. [Google Scholar] [CrossRef]
  10. Dang, H.; Cheng, Q.; Tian, Y.; Teng, C.; Xie, K.; Yan, L. Double pH-sensitive nanotheranostics of polypeptide nanoparticle encapsulated BODIPY with both NIR activated fluorescence and enhanced photodynamic therapy. J. Mater. Chem. B 2021, 9, 8871–8881. [Google Scholar] [CrossRef]
  11. Deng, K.; Chen, Y.; Li, C.; Deng, X.; Hou, Z.; Cheng, Z.; Han, Y.; Xing, B.; Lin, J. 808 nm light responsive nanotheranostic agents based on near-infrared dye functionalized manganese ferrite for magnetic-targeted and imaging-guided photodynamic/photothermal therapy. J. Mater. Chem. B 2017, 5, 1803–1814. [Google Scholar] [CrossRef] [PubMed]
  12. Zhou, S.; Li, D.; Lee, C.; Xie, J. Nanoparticle Phototherapy in the Era of Cancer Immunotherapy. Trends Chem. 2020, 2, 1082–1095. [Google Scholar] [CrossRef] [PubMed]
  13. Fu, Y.; Jang, M.-S.; Wang, N.; Li, Y.; Wu, T.P.; Lee, J.H.; Lee, D.S.; Yang, H.Y. Dual activatable self-assembled nanotheranostics for bioimaging and photodynamic therapy. J. Control. Release 2020, 327, 129–139. [Google Scholar] [CrossRef]
  14. Dou, Y.; Li, X.; Yang, W.; Guo, Y.; Wu, M.; Liu, Y.; Li, X.; Zhang, X.; Chang, J. PB@Au Core–Satellite Multifunctional Nanotheranostics for Magnetic Resonance and Computed Tomography Imaging in Vivo and Synergetic Photothermal and Radiosensitive Therapy. ACS Appl. Mater. Interfaces 2017, 9, 1263–1272. [Google Scholar] [CrossRef] [PubMed]
  15. Li, T.; Guo, L.; Li, J.; Mu, X.; Liu, L.; Song, S.; Luo, N.; Zhang, Q.; Zheng, B.; Jin, G. Precision USPIO-PEG-SLex Nanotheranostic Agent Targeted Photothermal Therapy for Enhanced Anti-PD-L1 Immunotherapy to Treat Immunotherapy Resistance. Int. J. Nanomed. 2024, 19, 1249–1272. [Google Scholar] [CrossRef] [PubMed]
  16. He, T.; He, J.; Younis, M.R.; Blum, N.T.; Lei, S.; Zhang, Y.; Huang, P.; Lin, J. Dual-Stimuli-Responsive Nanotheranostics for Dual-Targeting Photothermal-Enhanced Chemotherapy of Tumor. ACS Appl. Mater. Interfaces 2021, 13, 22204–22212. [Google Scholar] [CrossRef]
  17. Wan, Y.; Li, C.; Fu, L.; Feng, T.; Zhang, Y.; Li, Y.; Lin, J.; Huang, P.; Cui, D. Erythrocyte Membrane Camouflaged Nanotheranostics for Optical Molecular Imaging-Escorted Self-Oxygenation Photodynamic Therapy. Small 2024, 20, e2309026. [Google Scholar] [CrossRef]
  18. Ponzio, R.A.; Ibarra, L.E.; Achilli, E.E.; Odella, E.; Chesta, C.A.; Martínez, S.R.; Palacios, R.E. Sweet light o’ mine: Photothermal and photodynamic inactivation of tenacious pathogens using conjugated polymers. J. Photochem. Photobiol. B Biol. 2022, 234, 112510. [Google Scholar] [CrossRef]
  19. Han, Y.; Zhao, S.-J.; Wang, F.; Jiang, J.-H. In Situ Transformable Pro-nanotheranostic Platform for Activable Photoacoustic Imaging and Synergistic Photothermal/Chemodynamic Cancer Therapy. Anal. Chem. 2023, 95, 9453–9461. [Google Scholar] [CrossRef]
  20. Ding, X.; Liu, J.; Li, J.; Wang, F.; Wang, Y.; Song, S.; Zhang, H. Polydopamine coated manganese oxide nanoparticles with ultrahigh relaxivity as nanotheranostic agents for magnetic resonance imaging guided synergetic chemo-/photothermal therapy. Chem. Sci. 2016, 7, 6695–6700. [Google Scholar] [CrossRef]
  21. Du, C.; Qian, J.; Zhou, L.; Su, Y.; Zhang, R.; Dong, C.-M. Biopolymer–Drug Conjugate Nanotheranostics for Multimodal Imaging-Guided Synergistic Cancer Photothermal–Chemotherapy. ACS Appl. Mater. Interfaces 2017, 9, 31576–31588. [Google Scholar] [CrossRef] [PubMed]
  22. Hou, M.; Yan, C.; Chen, Z.; Zhao, Q.; Yuan, M.; Xu, Y.; Zhao, B. Multifunctional NIR-responsive poly(vinylpyrrolidone)-Cu-Sb-S nanotheranostic agent for photoacoustic imaging and photothermal/photodynamic therapy. Acta Biomater. 2018, 74, 334–343. [Google Scholar] [CrossRef] [PubMed]
  23. Yang, X.; Yu, Q.; Yang, N.; Xue, L.; Shao, J.; Li, B.; Shao, J.; Dong, X. Thieno[3,2-b]thiophene-DPP based near-infrared nanotheranostic agent for dual imaging-guided photothermal/photodynamic synergistic therapy. J. Mater. Chem. B 2019, 7, 2454–2462. [Google Scholar] [CrossRef]
  24. Yan, H.T.; Jang, M.-S.; Liu, C.; Fu, Q.; Wang, B.; Fu, Y.; Lee, J.H.; Yang, H.Y. Tumor microenvironment activated mussel-inspired hollow mesoporous nanotheranostic for enhanced synergistic photodynamic/chemodynamic therapy. J. Colloid Interface Sci. 2024, 665, 188–203. [Google Scholar] [CrossRef] [PubMed]
  25. Tian, Y.; Yi, W.; Shao, Q.; Ma, M.; Bai, L.; Song, R.; Zhang, P.; Si, J.; Hou, X.; Fan, J. Automatic-degradable Mo-doped W18O49 based nanotheranostics for CT/FL imaging guided synergistic chemo/photothermal/chemodynamic therapy. Chem. Eng. J. 2023, 462, 142156. [Google Scholar] [CrossRef]
  26. Wang, F.; Sun, Z.; Wang, Z.; Zhou, J.; Sun, L. PdAu-based nanotheranostic agent for photothermally initiated and oxygen-independent free radical generation. CrystEngComm 2022, 24, 5090–5096. [Google Scholar] [CrossRef]
  27. Li, J.; Jiang, R.; Wang, Q.; Li, X.; Hu, X.; Yuan, Y.; Lu, X.; Wang, W.; Huang, W.; Fan, Q. Semiconducting polymer nanotheranostics for NIR-II/Photoacoustic imaging-guided photothermal initiated nitric oxide/photothermal therapy. Biomaterials 2019, 217, 119304. [Google Scholar] [CrossRef]
  28. Wu, J.; Bremner, D.H.; Niu, S.; Shi, M.; Wang, H.; Tang, R.; Zhu, L.-M. Chemodrug-Gated Biodegradable Hollow Mesoporous Organosilica Nanotheranostics for Multimodal Imaging-Guided Low-Temperature Photothermal Therapy/Chemotherapy of Cancer. ACS Appl. Mater. Interfaces 2018, 10, 42115–42126. [Google Scholar] [CrossRef]
  29. Xu, C.; Gao, F.; Wu, J.; Niu, S.; Li, F.; Jin, L.; Shi, Q.; Du, L. Biodegradable nanotheranostics with hyperthermia-induced bubble ability for ultrasound imaging-guided chemo-photothermal therapy. Int. J. Nanomed. 2019, 14, 7141–7153. [Google Scholar] [CrossRef]
  30. Zhou, C.; Zhang, L.; Sun, T.; Zhang, Y.; Liu, Y.; Gong, M.; Xu, Z.; Du, M.; Liu, Y.; Liu, G.; et al. Activatable NIR-II Plasmonic Nanotheranostics for Efficient Photoacoustic Imaging and Photothermal Cancer Therapy. Adv. Mater. 2021, 33, e2006532. [Google Scholar] [CrossRef]
  31. Wang, R.; Wang, J.; Wang, X.; Song, G.; Ye, L.; Gu, W. BSA-templated ultrasmall Ag/Gd2O3 as a self-enabled nanotheranostic for MR/CT/PA tri-modality imaging and photothermal therapy. Biomater. Sci. 2022, 10, 4508–4514. [Google Scholar] [CrossRef] [PubMed]
  32. Wu, B.; Lu, S.-T.; Yu, H.; Liao, R.-F.; Li, H.; Lucie Zafitatsimo, B.V.; Li, Y.-S.; Zhang, Y.; Zhu, X.-L.; Liu, H.-G.; et al. Gadolinium-chelate functionalized bismuth nanotheranostic agent for in vivo MRI/CT/PAI imaging-guided photothermal cancer therapy. Biomaterials 2018, 159, 37–47. [Google Scholar] [CrossRef] [PubMed]
  33. Xiao, Q.; Zheng, X.; Bu, W.; Ge, W.; Zhang, S.; Chen, F.; Xing, H.; Ren, Q.; Fan, W.; Zhao, K.; et al. A Core/Satellite Multifunctional Nanotheranostic for in Vivo Imaging and Tumor Eradication by Radiation/Photothermal Synergistic Therapy. J. Am. Chem. Soc. 2013, 135, 13041–13048. [Google Scholar] [CrossRef]
  34. Zheng, Z.; Jia, Z.; Qin, Y.; Dai, R.; Chen, X.; Ma, Y.; Xie, X.; Zhang, R. All-in-One Zeolite–Carbon-Based Nanotheranostics with Adjustable NIR-II Window Photoacoustic/Fluorescence Imaging Performance for Precise NIR-II Photothermal-Synergized Catalytic Antitumor Therapy. Small 2021, 17, 2103252. [Google Scholar] [CrossRef] [PubMed]
  35. Zhou, B.; Yin, C.; Feng, Q.; Wu, Y.; Pan, X.; Liu, C.; Tian, J.; Geng, S.; Wang, K.; Xing, J.; et al. Polypyrrole-based nanotheranostic agent for MRI guided photothermal-chemodynamic synergistic cancer therapy. Nanoscale 2021, 13, 19085–19097. [Google Scholar] [CrossRef]
  36. Fang, X.; Lui, K.-H.; Li, S.; Lo, W.-S.; Li, X.; Gu, Y.; Wong, W.-T. Multifunctional Nanotheranostic Gold Nanocage/Selenium Core-Shell for PAI-Guided Chemo-Photothermal Synergistic Therapy in vivo. Int. J. Nanomed. 2020, 15, 10271–10284. [Google Scholar] [CrossRef]
  37. Chuang, Y.-C.; Hsia, Y.; Chu, C.-H.; Maharajan, S.; Hsu, F.-C.; Lee, H.-L.; Chiou, J.F.; Ch’ang, H.-J.; Liao, L.-D.; Lo, L.-W. Photothermal Temperature-Modulated Cancer Metastasis Harnessed Using Proteinase-Triggered Assembly of Near-Infrared II Photoacoustic/Photothermal Nanotheranostics. ACS Appl. Mater. Interfaces 2024, 16, 40611–40627. [Google Scholar] [CrossRef]
  38. Eyvazzadeh, N.; Shakeri-Zadeh, A.; Fekrazad, R.; Amini, E.; Ghaznavi, H.; Kamrava, S.K. Gold-coated magnetic nanoparticle as a nanotheranostic agent for magnetic resonance imaging and photothermal therapy of cancer. Lasers Med. Sci. 2017, 32, 1469–1477. [Google Scholar] [CrossRef]
  39. Gao, C.; Jian, J.; Luo, L.; Liang, J.; Li, Z.; Pang, M.; Cai, H.; Shen, X.-C. Single-walled carbon nanohorns-based smart nanotheranostic: From phototherapy to enzyme-activated fluorescence imaging-guided photodynamic therapy. J. Colloid Interface Sci. 2022, 628, 273–286. [Google Scholar] [CrossRef]
  40. Qu, B.; Li, X.; Zhang, X.; Li, W.; Zhang, R. PVP-coated Sb2Se3 nanorods as nanotheranostic agents for photoacoustic imaging and photothermal therapy in NIR-I bio-windows. RSC Adv. 2020, 10, 15221–15227. [Google Scholar] [CrossRef]
  41. Thakur, N.S.; Patel, G.; Kushwah, V.; Jain, S.; Banerjee, U.C. Facile development of biodegradable polymer-based nanotheranostics: Hydrophobic photosensitizers delivery, fluorescence imaging and photodynamic therapy. J. Photochem. Photobiol. B Biol. 2019, 193, 39–50. [Google Scholar] [CrossRef]
  42. Liu, J.; Cheng, D.; Zhu, A.; Ding, M.; Yu, N.; Li, J. Neutrophil-Targeting Semiconducting Polymer Nanotheranostics for NIR-II Fluorescence Imaging-Guided Photothermal-NO-Immunotherapy of Orthotopic Glioblastoma. Adv. Sci. 2024, 11, e2406750. [Google Scholar] [CrossRef] [PubMed]
  43. Liu, T.; Zhang, M.; Liu, W.; Zeng, X.; Song, X.; Yang, X.; Zhang, X.; Feng, J. Metal Ion/Tannic Acid Assembly as a Versatile Photothermal Platform in Engineering Multimodal Nanotheranostics for Advanced Applications. ACS Nano 2018, 12, 3917–3927. [Google Scholar] [CrossRef] [PubMed]
  44. Wang, S.; Yang, Y.; Wu, H.; Li, J.; Xie, P.; Xu, F.; Zhou, L.; Zhao, J.; Chen, H. Thermosensitive and tum or microenvironment activated nanotheranostics for the chemodynamic/photothermal therapy of colorectal tumor. J. Colloid Interface Sci. 2021, 612, 223–234. [Google Scholar] [CrossRef] [PubMed]
  45. Goel, S.; Ferreira, C.A.; Chen, F.; Ellison, P.A.; Siamof, C.M.; Barnhart, T.E.; Cai, W. Activatable Hybrid Nanotheranostics for Tetramodal Imaging and Synergistic Photothermal/Photodynamic Therapy. Adv. Mater. 2017, 30, 1704367. [Google Scholar] [CrossRef]
  46. Fan, W.; Shen, B.; Bu, W.; Chen, F.; He, Q.; Zhao, K.; Zhang, S.; Zhou, L.; Peng, W.; Xiao, Q.; et al. A smart upconversion-based mesoporous silica nanotheranostic system for synergetic chemo-/radio-/photodynamic therapy and simultaneous MR/UCL imaging. Biomaterials 2014, 35, 8992–9002. [Google Scholar] [CrossRef]
  47. Fan, Z.; Ren, L.; Zhang, W.; Li, D.; Zhao, G.; Yu, J. AIE luminogen-functionalised mesoporous silica nanoparticles as nanotheranostic agents for imaging guided synergetic chemo-/photothermal therapy. Inorg. Chem. Front. 2017, 4, 833–839. [Google Scholar] [CrossRef]
  48. Liu, W.; Miao, W.; Li, Y.; He, D.; Tang, Y.; Guan, X.; Li, C.; Wu, F.; Tang, J.; Wang, S. Hybridized double-shell periodic mesoporous organosilica nanotheranostics for ultrasound imaging guided photothermal therapy. J. Colloid Interface Sci. 2021, 608, 2964–2972. [Google Scholar] [CrossRef]
  49. Wang, X.; Wang, Z.; Ma, W.; Wu, X.; Fang, W.; Guo, C.; Jin, Y. Construction of a nanotheranostic system Zr-MOF@PPa/AF@PEG for improved photodynamic therapy effects based on the PDT-oxygen consumption and hypoxia sensitive chemotherapeutic drug. J. Photochem. Photobiol. B Biol. 2021, 222, 112274. [Google Scholar] [CrossRef]
  50. Wang, K.; Zhuang, J.; Chen, L.; Xu, D.; Zhang, X.; Chen, Z.; Wei, Y.; Zhang, Y. One-pot synthesis of AIE based bismuth sulfide nanotheranostics for fluorescence imaging and photothermal therapy. Colloids Surfaces B Biointerfaces 2017, 160, 297–304. [Google Scholar] [CrossRef]
  51. Wang, K.; Fan, X.; Zhao, L.; Zhang, X.; Zhang, X.; Li, Z.; Yuan, Q.; Zhang, Q.; Huang, Z.; Xie, W.; et al. Aggregation Induced Emission Fluorogens Based Nanotheranostics for Targeted and Imaging-Guided Chemo-Photothermal Combination Therapy. Small 2016, 12, 6568–6575. [Google Scholar] [CrossRef] [PubMed]
  52. Yong, Y.; Cheng, X.; Bao, T.; Zu, M.; Yan, L.; Yin, W.; Ge, C.; Wang, D.; Gu, Z.; Zhao, Y. Tungsten Sulfide Quantum Dots as Multifunctional Nanotheranostics for In Vivo Dual-Modal Image-Guided Photothermal/Radiotherapy Synergistic Therapy. ACS Nano 2015, 9, 12451–12463. [Google Scholar] [CrossRef] [PubMed]
  53. Yu, J.; Yin, W.; Zheng, X.; Tian, G.; Zhang, X.; Bao, T.; Dong, X.; Wang, Z.; Gu, Z.; Ma, X.; et al. Smart MoS2/Fe3O4 Nanotheranostic for Magnetically Targeted Photothermal Therapy Guided by Magnetic Resonance/Photoacoustic Imaging. Theranostics 2015, 5, 931–945. [Google Scholar] [CrossRef] [PubMed]
  54. Li, T.; Liu, L.; Xu, P.; Yuan, P.; Tian, Y.; Cheng, Q.; Yan, L. Multifunctional Nanotheranostic Agent for NIR-II Imaging-Guided Synergetic Photothermal/Photodynamic Therapy. Adv. Ther. 2020, 4, 2000240. [Google Scholar] [CrossRef]
  55. Huang, M.; Xu, C.; Yang, S.; Zhang, Z.; Wei, Z.; Wu, M.; Xue, F. Vehicle-Free Nanotheranostic Self-Assembled from Clinically Approved Dyes for Cancer Fluorescence Imaging and Photothermal/Photodynamic Combinational Therapy. Pharmaceutics 2022, 14, 1074. [Google Scholar] [CrossRef]
  56. Jia, H.-R.; Jiang, Y.-W.; Zhu, Y.-X.; Li, Y.-H.; Wang, H.-Y.; Han, X.; Yu, Z.-W.; Gu, N.; Liu, P.; Chen, Z.; et al. Plasma membrane activatable polymeric nanotheranostics with self-enhanced light-triggered photosensitizer cellular influx for photodynamic cancer therapy. J. Control. Release 2017, 255, 231–241. [Google Scholar] [CrossRef]
  57. Yang, Z.; He, W.; Zheng, H.; Wei, J.; Liu, P.; Zhu, W.; Lin, L.; Zhang, L.; Yi, C.; Xu, Z.; et al. One-pot synthesis of albumin-gadolinium stabilized polypyrrole nanotheranostic agent for magnetic resonance imaging guided photothermal therapy. Biomaterials 2018, 161, 1–10. [Google Scholar] [CrossRef]
  58. Du, K.M.; Lei, P.P.; Dong, L.L.; Zhang, M.L.; Gao, X.; Yao, S.; Feng, J.; Zhang, H.J. In situ decorating of ultrasmall Ag2Se on upconversion nanoparticles as novel nanotheranostic agent for multimodal imaging-guided cancer photothermal therapy. Appl. Mater. Today 2020, 18, 15. [Google Scholar] [CrossRef]
  59. Gao, J.; Sanchez-Purra, M.; Huang, H.; Wang, S.; Chen, Y.; Yu, X.; Luo, Q.; Hamad-Schifferli, K.; Liu, S. Synthesis of different-sized gold nanostars for Raman bioimaging and photothermal therapy in cancer nanotheranostics. Sci. China Chem. 2017, 60, 1219–1229. [Google Scholar] [CrossRef]
  60. Hong, T.; Jiang, Y.; Yue, Z.; Song, X.; Wang, Z.; Zhang, S. Construction of Multicolor Upconversion Nanotheranostic Agent for in-situ Cooperative Photodynamic Therapy for Deep-Seated Malignant Tumors. Front. Chem. 2020, 8, 52. [Google Scholar] [CrossRef]
  61. Xiu, W.; Gan, S.; Wen, Q.; Qiu, Q.; Dai, S.; Dong, H.; Li, Q.; Yuwen, L.; Weng, L.; Teng, Z.; et al. Biofilm Microenvironment-Responsive Nanotheranostics for Dual-Mode Imaging and Hypoxia-Relief-Enhanced Photodynamic Therapy of Bacterial Infections. Research 2020, 2020, 9426453. [Google Scholar] [CrossRef]
  62. Guo, Y.; Ran, Y.; Wang, Z.; Cheng, J.; Cao, Y.; Yang, C.; Liu, F.; Ran, H. Magnetic-responsive and targeted cancer nanotheranostics by PA/MR bimodal imaging-guided photothermally triggered immunotherapy. Biomaterials 2019, 219, 119370. [Google Scholar] [CrossRef] [PubMed]
  63. Zhang, Y.; Song, T.; Feng, T.; Wan, Y.; Blum, N.T.; Liu, C.; Zheng, C.; Zhao, Z.; Jiang, T.; Wang, J.; et al. Plasmonic modulation of gold nanotheranostics for targeted NIR-II photothermal-augmented immunotherapy. Nano Today 2020, 35, 100987. [Google Scholar] [CrossRef]
  64. Guo, Z.; Xie, W.; Lu, J.; Guo, X.; Chi, Y.; Wang, D.; Takuya, N.; Xu, W.; Ye, J.; Liu, X.; et al. Ferrous ions doped layered double hydroxide: Smart 2D nanotheranostic platform with imaging-guided synergistic chemo/photothermal therapy for breast cancer. Biomater. Sci. 2021, 9, 5928–5938. [Google Scholar] [CrossRef]
  65. Zhang, R.; Liu, M.; Liu, S.; Liang, X.; Lu, R.; Shuai, X.; Wu, D.; Cao, Z. Holmium (III)-doped multifunctional nanotheranostic agent for ultra-high-field magnetic resonance imaging-guided chemo-photothermal tumor therapy. Acta Biomater. 2023, 172, 454–465. [Google Scholar] [CrossRef] [PubMed]
  66. Zhang, Y.; Wan, Y.; Chen, Y.; Blum, N.T.; Lin, J.; Huang, P. Ultrasound-Enhanced Chemo-Photodynamic Combination Therapy by Using Albumin “Nanoglue”-Based Nanotheranostics. ACS Nano 2020, 14, 5560–5569. [Google Scholar] [CrossRef]
  67. Ding, F.; Liu, J.; Ai, K.; Xu, C.; Mao, X.; Liu, Z.; Xiao, H. Simultaneous Activation of Pyroptosis and cGAS-STING Pathway with Epigenetic/Photodynamic Nanotheranostic for Enhanced Tumor Photoimmunotherapy. Adv. Mater. 2023, 36, e2306419. [Google Scholar] [CrossRef]
  68. Li, X.; Yu, S.; Lee, D.; Kim, G.; Lee, B.; Cho, Y.; Zheng, B.-Y.; Ke, M.-R.; Huang, J.-D.; Nam, K.T.; et al. Facile Supramolecular Approach to Nucleic-Acid-Driven Activatable Nanotheranostics That Overcome Drawbacks of Photodynamic Therapy. ACS Nano 2018, 12, 681–688. [Google Scholar] [CrossRef]
  69. Du, C.; Ding, Y.; Qian, J.; Zhang, R.; Dong, C.-M.; Du, C.; Ding, Y.; Qian, J.; Zhang, R.; Dong, C.-M.; et al. Dual drug-paired polyprodrug nanotheranostics reverse multidrug resistant cancers via mild photothermal-cocktail chemotherapy. J. Mater. Chem. B 2019, 7, 5306–5319. [Google Scholar] [CrossRef]
  70. Ren, Q.; Sheng, Y.; Tao, C.; Niu, S.; Yu, N.; Chen, Z.; Lian, W. Zinc peroxide-based nanotheranostic platform with endogenous hydrogen peroxide/oxygen generation for enhanced photodynamic-chemo therapy of tumors. J. Colloid Interface Sci. 2024, 668, 88–97. [Google Scholar] [CrossRef]
  71. Li, Y.; Mu, X.; Feng, W.; Gao, M.; Wang, Z.; Bai, X.; Ren, X.; Lu, Y.; Zhou, X. Supramolecular prodrug-like nanotheranostics with dynamic and activatable nature for synergistic photothermal immunotherapy of metastatic cancer. J. Control. Release 2024, 367, 354–365. [Google Scholar] [CrossRef] [PubMed]
  72. Wang, X.; Yuan, Y.; Wu, Z.; Jiang, J.-H. Self-Tracking Multifunctional Nanotheranostics for Sensitive miRNA Imaging Guided Photodynamic Therapy. ACS Appl. Bio Mater. 2020, 3, 2597–2603. [Google Scholar] [CrossRef] [PubMed]
  73. Nagy-Simon, T.; Potara, M.; Craciun, A.-M.; Licarete, E.; Astilean, S. IR780-dye loaded gold nanoparticles as new near infrared activatable nanotheranostic agents for simultaneous photodynamic and photothermal therapy and intracellular tracking by surface enhanced resonant Raman scattering imaging. J. Colloid Interface Sci. 2018, 517, 239–250. [Google Scholar] [CrossRef] [PubMed]
  74. Xu, X.; Chong, Y.; Liu, X.; Fu, H.; Yu, C.; Huang, J.; Zhang, Z. Multifunctional nanotheranostic gold nanocages for photoacoustic imaging guided radio/photodynamic/photothermal synergistic therapy. Acta Biomater. 2019, 84, 328–338. [Google Scholar] [CrossRef]
  75. Zhu, H.; Fang, Y.; Miao, Q.; Qi, X.; Ding, D.; Chen, P.; Pu, K. Regulating Near-Infrared Photodynamic Properties of Semiconducting Polymer Nanotheranostics for Optimized Cancer Therapy. ACS Nano 2017, 11, 8998–9009. [Google Scholar] [CrossRef]
  76. Liu, Y.; Shu, G.; Li, X.; Chen, H.; Zhang, B.; Pan, H.; Li, T.; Gong, X.; Wang, H.; Wu, X.; et al. Human HSP70 Promoter-Based Prussian Blue Nanotheranostics for Thermo-Controlled Gene Therapy and Synergistic Photothermal Ablation. Adv. Funct. Mater. 2018, 28, 1802026. [Google Scholar] [CrossRef]
  77. Hu, X.; Tang, Y.; Hu, Y.; Lu, F.; Lu, X.; Wang, Y.; Li, J.; Li, Y.; Ji, Y.; Wang, W.; et al. Gadolinium-Chelated Conjugated Polymer-Based Nanotheranostics for Photoacoustic/Magnetic Resonance/NIR-II Fluorescence Imaging-Guided Cancer Photothermal Therapy. Theranostics 2019, 9, 4168–4181. [Google Scholar] [CrossRef]
  78. Yang, W.T.; Guo, W.S.; Le, W.J.; Lv, G.X.; Zhang, F.H.; Shi, L.; Wang, X.L.; Wang, J.; Wang, S.; Chang, J.; et al. Albumin-Bioinspired Gd:CuS Nanotheranostic Agent for In Vivo Photoacoustic/Magnetic Resonance Imaging-Guided Tumor-Targeted Photothermal Therapy. ACS Nano 2016, 10, 10245–10257. [Google Scholar] [CrossRef]
  79. Zhu, Y.; Deng, M.; Xu, N.; Xie, Y.; Zhang, X. A Tumor Microenvironment Responsive Nanotheranostics Agent for Magnetic Resonance Imaging and Synergistic Photodynamic Therapy/Photothermal Therapy of Liver Cancer. Front. Chem. 2021, 9, 650899. [Google Scholar] [CrossRef]
  80. Fu, L.; Wan, Y.; Li, C.; Qi, C.; He, T.; Yang, C.; Zhang, Y.; Lin, J.; Huang, P. Biodegradable Calcium Phosphate Nanotheranostics with Tumor-Specific Activatable Cascade Catalytic Reactions-Augmented Photodynamic Therapy. Adv. Funct. Mater. 2021, 31, 2009848. [Google Scholar] [CrossRef]
  81. Nuthalapati, K.; Vankayala, R.; Shanmugam, M.; Thangudu, S.; Chiang, C.; Hwang, K.C. Engineering Tumor-Specific Nanotheranostic Agent with MR Image-Guided NIR-II & -III Photodynamic Therapy to Combat Against Deeply Seated Orthotopic Glioblastoma. Small Sci. 2024, 4, 2400191. [Google Scholar] [CrossRef]
  82. Tao, Y.; Yan, C.; Wu, Y.; Li, D.; Li, J.; Xie, Y.; Cheng, Y.; Xu, Y.; Yang, K.; Zhu, W.; et al. Uniting Dual-Modal MRI/Chemiluminescence Nanotheranostics: Spatially and Sensitively Self-Reporting Photodynamic Therapy in Oral Cancer. Adv. Funct. Mater. 2023, 33, 2303240. [Google Scholar] [CrossRef]
  83. Wang, Z.; Zhen, X.; Upputuri, P.K.; Jiang, Y.; Lau, J.; Pramanik, M.; Pu, K.; Xing, B. Redox-Activatable and Acid-Enhanced Nanotheranostics for Second Near-Infrared Photoacoustic Tomography and Combined Photothermal Tumor Therapy. ACS Nano 2019, 13, 5816–5825. [Google Scholar] [CrossRef] [PubMed]
  84. Xiao, Y.; Xiang, C.; Li, S.; Mao, C.; Chen, H.; Chen, J.; Tian, S.; Cui, X.; Wan, Y.; Huang, Z.; et al. Single-Photomolecular Nanotheranostics for Synergetic Near-Infrared Fluorescence and Photoacoustic Imaging-Guided Highly Effective Photothermal Ablation. Small 2020, 16, e2002672. [Google Scholar] [CrossRef] [PubMed]
  85. Zhao, C.; Liu, W.; Sun, W.; Yu, H.; Sheng, Z.; Wang, J.; Jiang, Y.; Liu, Y. Activatable self-assembled organic nanotheranostics: Aspartyl aminopeptidase triggered NIR fluorescence imaging-guided photothermal/photodynamic synergistic therapy. Anal. Chim. Acta 2022, 1231, 340198. [Google Scholar] [CrossRef]
  86. Li, S.; Lui, K.-H.; Lau, W.-S.; Chen, J.; Lo, W.-S.; Li, X.; Gu, Y.-J.; Lin, L.-T.; Wong, W.-T. MSOT-Guided Nanotheranostics for Synergistic Mild Photothermal Therapy and Chemotherapy to Boost Necroptosis/Apoptosis. ACS Appl. Mater. Interfaces 2022, 14, 33712–33725. [Google Scholar] [CrossRef]
  87. Li, X.; Zhang, D.; Yin, C.; Lu, G.; Wan, Y.; Huang, Z.; Tan, J.; Li, S.; Luo, J.; Lee, C.-S. A Diradicaloid Small Molecular Nanotheranostic with Strong Near-Infrared Absorbance for Effective Cancer Photoacoustic Imaging and Photothermal Therapy. ACS Appl. Mater. Interfaces 2021, 13, 15983–15991. [Google Scholar] [CrossRef]
  88. Wang, S.; Zhang, Q.; Luo, X.F.; Li, J.; He, H.; Yang, F.; Di, Y.; Jin, C.; Jiang, X.G.; Shen, S.; et al. Magnetic graphene-based nanotheranostic agent for dual-modality mapping guided photothermal therapy in regional lymph nodal metastasis of pancreatic cancer. Biomaterials 2014, 35, 9473–9483. [Google Scholar] [CrossRef]
  89. Ren, S.; Dai, R.; Zheng, Z.; Chen, X.; Wu, S.; Zhang, R.; Gui, Z. Multifunctional AuPd-cluster nanotheranostic agents with a cascade self-regulating redox tumor-microenvironment for dual-photodynamic synergized enzyme catalytic therapy. J. Mater. Chem. B 2022, 11, 109–118. [Google Scholar] [CrossRef]
  90. Lu, Y.-J.; S., A.T.; Chuang, C.-C.; Chen, J.-P. Liposomal IR-780 as a Highly Stable Nanotheranostic Agent for Improved Photothermal/Photodynamic Therapy of Brain Tumors by Convection-Enhanced Delivery. Cancers 2021, 13, 3690. [Google Scholar] [CrossRef]
  91. Yue, Z.; Hong, T.; Song, X.; Wang, Z. Construction of a targeted photodynamic nanotheranostic agent using upconversion nanoparticles coated with an ultrathin silica layer. Chem. Commun. 2018, 54, 10618–10621. [Google Scholar] [CrossRef] [PubMed]
  92. Zhang, M.; Zhang, Y.; Hang, L.; Zhang, T.; Luo, C.; Li, W.; Sun, Y.; Wen, H.; Chen, Y.; Jiang, G.; et al. Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy. Nanoscale 2024, 16, 6095–6108. [Google Scholar] [CrossRef] [PubMed]
  93. Wang, Y.; Zu, M.; Ma, X.; Jia, D.; Lu, Y.; Zhang, T.; Xue, P.; Kang, Y.; Xu, Z. Glutathione-Responsive Multifunctional “Trojan Horse” Nanogel as a Nanotheranostic for Combined Chemotherapy and Photodynamic Anticancer Therapy. ACS Appl. Mater. Interfaces 2020, 12, 50896–50908. [Google Scholar] [CrossRef] [PubMed]
  94. Wang, F.; Li, N.; Wang, W.; Ma, L.; Sun, Y.; Wang, H.; Zhan, J.; Yu, D. A Multifunctional, Highly Biocompatible, and Double-Triggering Caramelized Nanotheranostic System Loaded with Fe3O4 and DOX for Combined Chemo-Photothermal Therapy and Real-Time Magnetic Resonance Imaging Monitoring of Triple Negative Breast Cancer. Int. J. Nanomed. 2023, 18, 881–897. [Google Scholar] [CrossRef]
  95. Yang, J.; Ren, B.; Yin, X.; Xiang, L.; Hua, Y.; Huang, X.; Wang, H.; Mao, Z.; Chen, W.; Deng, J. Expanded ROS Generation and Hypoxia Reversal: Excipient-free Self-assembled Nanotheranostics for Enhanced Cancer Photodynamic Immunotherapy. Adv. Mater. 2024, 36, e2402720. [Google Scholar] [CrossRef]
  96. Wang, B.; Dai, Y.; Kong, Y.; Du, W.; Ni, H.; Zhao, H.; Sun, Z.; Shen, Q.; Li, M.; Fan, Q. Tumor Microenvironment-Responsive Fe(III)–Porphyrin Nanotheranostics for Tumor Imaging and Targeted Chemodynamic–Photodynamic Therapy. ACS Appl. Mater. Interfaces 2020, 12, 53634–53645. [Google Scholar] [CrossRef]
  97. Park, D.; Ahn, K.-O.; Jeong, K.-C.; Choi, Y. Polypyrrole-based nanotheranostics for activatable fluorescence imaging and chemo/photothermal dual therapy of triple-negative breast cancer. Nanotechnology 2016, 27, 185102. [Google Scholar] [CrossRef]
  98. Liu, Q.; Liu, L.; Mo, C.; Zhou, X.; Chen, D.; He, Y.; He, H.; Kang, W.; Zhao, Y.; Jin, G. Polyethylene glycol-coated ultrasmall superparamagnetic iron oxide nanoparticles-coupled sialyl Lewis X nanotheranostic platform for nasopharyngeal carcinoma imaging and photothermal therapy. J. Nanobiotechnol. 2021, 19, 171. [Google Scholar] [CrossRef]
  99. Shou, P.; Yu, Z.; Wu, Y.; Feng, Q.; Zhou, B.; Xing, J.; Liu, C.; Tu, J.; Akakuru, O.U.; Ye, Z.; et al. Zn2+ Doped Ultrasmall Prussian Blue Nanotheranostic Agent for Breast Cancer Photothermal Therapy under MR Imaging Guidance. Adv. Healthc. Mater. 2019, 9, e1900948. [Google Scholar] [CrossRef]
  100. Ni, D.; Ferreira, C.A.; Barnhart, T.E.; Quach, V.; Yu, B.; Jiang, D.; Wei, W.; Liu, H.; Engle, J.W.; Hu, P.; et al. Magnetic Targeting of Nanotheranostics Enhances Cerenkov Radiation-Induced Photodynamic Therapy. J. Am. Chem. Soc. 2018, 140, 14971–14979. [Google Scholar] [CrossRef]
  101. Liu, Z.; Wang, P.; Xie, F.; Chen, J.; Cai, M.; Li, Y.; Yan, J.; Lin, Q.; Luo, F. Virus-Inspired Hollow Mesoporous Gadolinium-Bismuth Nanotheranostics for Magnetic Resonance Imaging-Guided Synergistic Photodynamic-Radiotherapy. Adv. Healthc. Mater. 2021, 11, 2102060. [Google Scholar] [CrossRef] [PubMed]
  102. Yang, H.Y.; Jang, M.-S.; Li, Y.; Fu, Y.; Wu, T.P.; Lee, J.H.; Lee, D.S. Hierarchical tumor acidity-responsive self-assembled magnetic nanotheranostics for bimodal bioimaging and photodynamic therapy. J. Control. Release 2019, 301, 157–165. [Google Scholar] [CrossRef] [PubMed]
  103. Li, X.; Sun, X.; Wang, Y.; Chen, H.; Gao, Y. A nanotheranostics with hypoxia-switchable fluorescence and photothermal effect for hypoxia imaging-guided immunosuppressive tumor microenvironment modulation. J. Colloid Interface Sci. 2024, 678, 897–912. [Google Scholar] [CrossRef] [PubMed]
  104. Zou, J.; Xue, L.; Yang, N.; Ren, Y.; Fan, Z.; Wang, W.; Si, W.; Zhang, Y.; Huang, W.; Dong, X. A glutathione responsive pyrrolopyrrolidone nanotheranostic agent for turn-on fluorescence imaging guided photothermal/photodynamic cancer therapy. Mater. Chem. Front. 2019, 3, 2143–2150. [Google Scholar] [CrossRef]
  105. Zhu, W.; Zhang, L.; Yang, Z.; Liu, P.; Wang, J.; Cao, J.; Shen, A.; Xu, Z. An efficient tumor-inducible nanotheranostics for magnetic resonance imaging and enhanced photodynamic therapy. Chem. Eng. J. 2018, 358, 969–979. [Google Scholar] [CrossRef]
  106. Zhao, Y.; Liu, Y.; Wang, Y.; Xu, B.; Zhang, S.; Liu, J.; Zhang, T.; Jin, L.; Song, S.; Zhang, H. Rapidly clearable MnCo2O4@PAA as novel nanotheranostic agents for T1/T2 bimodal MRI imaging-guided photothermal therapy. Nanoscale 2021, 13, 16251–16257. [Google Scholar] [CrossRef]
  107. Huang, K.; Li, F.; Yuan, K.; Yang, Y.; Chang, H.; Liang, Y.; Yan, X.; Zhao, J.; Tang, T.; Yang, S. A MOF-armored zinc-peroxide nanotheranostic platform for eradicating drug resistant bacteria via image-guided and in situ activated photodynamic therapy. Appl. Mater. Today 2022, 28, 101513. [Google Scholar] [CrossRef]
  108. Yang, C.; Che, X.; Zhang, Y.; Gu, D.; Dai, G.; Shu, J.; Yang, L. Hybrid FeWO4-Hyaluronic Acid Nanoparticles as a Targeted Nanotheranostic Agent for Multimodal Imaging-Guided Tumor Photothermal Therapy. Int. J. Nanomed. 2023, 18, 8023–8037. [Google Scholar] [CrossRef]
  109. Yang, C.; Tian, S.; Qiu, W.; Mo, L.; Lin, W. Hierarchical MOF@AuNP/Hairpin Nanotheranostic for Enhanced Photodynamic Therapy via O2 Self-Supply and Cancer-Related MicroRNA Imaging In Vivo. Anal. Chem. 2023, 95, 16279–16288. [Google Scholar] [CrossRef]
  110. Zou, Y.; Jin, H.; Sun, F.; Dai, X.; Xu, Z.; Yang, S.; Liao, G. Design and Synthesis of a Lead Sulfide Based Nanotheranostic Agent for Computer Tomography/Magnetic Resonance Dual-Mode-Bioimaging-Guided Photothermal Therapy. ACS Appl. Nano Mater. 2018, 1, 2294–2305. [Google Scholar] [CrossRef]
Jnt 05 00014 g001
Figure 1. Schematic representation of the fabrication process of HA-IR808-SWNHs and the programmed treatment of tumors. Reprinted with permission from Ref. [39]. 2022, Elsevier.
Figure 1. Schematic representation of the fabrication process of HA-IR808-SWNHs and the programmed treatment of tumors. Reprinted with permission from Ref. [39]. 2022, Elsevier.
Jnt 05 00014 g001
Jnt 05 00014 g002
Figure 2. Imaging-guided photothermal-triggered immunotherapy using magnetic-responsive nanoagents (MINPs) stimulates immune responses to target both primary and distant untreated tumors. Reprinted with permission from Ref. [62], 2019, Elsevier.
Figure 2. Imaging-guided photothermal-triggered immunotherapy using magnetic-responsive nanoagents (MINPs) stimulates immune responses to target both primary and distant untreated tumors. Reprinted with permission from Ref. [62], 2019, Elsevier.
Jnt 05 00014 g002
Jnt 05 00014 g003
Figure 3. Schematic illustration of the design and preparation of Cy7-TCF-SS-NLG PNAs for synergistic treatments, which include photothermal therapy and checkpoint blockade immunotherapy. Reprinted with permission from Ref. [71], 2024, Elsevier.
Figure 3. Schematic illustration of the design and preparation of Cy7-TCF-SS-NLG PNAs for synergistic treatments, which include photothermal therapy and checkpoint blockade immunotherapy. Reprinted with permission from Ref. [71], 2024, Elsevier.
Jnt 05 00014 g003
Table 1. Imaging modalities and functional materials for cancer therapy.
Table 1. Imaging modalities and functional materials for cancer therapy.
Imaging ModalityShort DescriptionRef.
Organics
Conjugated Polymer, Thermosensitive Nitric Oxide DonorNIR-II ImagingEnables hyperthermia and NO release, enhancing tumor ablation.[2]
Polypeptide-Encapsulated Boron-Dipyrromethene (BODIPY)Fluorescence ImagingpH-sensitive fluorescence enhancement and lysosome targeting with high singlet oxygen quantum yield.[10]
Polypeptide-Coated BODIPY Polymer Micelles (P@BDP)NIR ImagingDual NIR-I/NIR-II imaging with ROS production for tumor ablation.[54]
Indocyanine Green and Methylene BlueFluorescence, PTTHigh photothermal conversion and singlet oxygen generation, with minimal toxicity.[55]
Protoporphyrin IX-Conjugated Glycol ChitosanFluorescence and ROS ImagingPlasma membrane targeting with prolonged tumor retention and imaging-guided therapy.[56]
Albumin-Gadolinium Stabilized Polypyrrole (PPy@BSA-Gd)MRI ImagingEfficient photothermal conversion, high cytocompatibility, and effective MRI-guided tumor therapy.[57]
Polydopamine-Coated Hollow Mesoporous OrganosilicaFluorescence and Chemo/Photothermal TherapyControlled DOX release, high imaging quality, and effective therapy under dual-mode imaging.[29]
Inorganics
Gadolinium Oxide (Gd2O3), Iridium Oxide (IrO2)MR/CT ImagingHigh relaxivity and X-ray attenuation for enhanced imaging and therapeutic effects.[1]
Gold Nanorods (GNRs)Photoacoustic Imaging (PA)Immune checkpoint inhibition and enhanced photothermal therapy for efficient tumor suppression.[3]
Gold Nanoparticles (GNPs)MR and Optical ImagingSelective cancer cell destruction, with minimal damage to healthy cells.[7]
Gadolinium-Encapsulated Graphene Carbon NanoparticlesMRI and Fluorescence ImagingHigh relaxivity, renal clearance, and minimal toxicity.[8]
Gold Nanodandelions (GNDs) with GelatinPA/PTT ImagingMultibranched structure activated by tumor acidity for photothermal conversion and metastasis control.[36]
Silver Selenide Nanodots on UCNPsTetra-Modal ImagingHigh X-ray attenuation and excellent biocompatibility.[58]
Zinc Sulfide and Cuprous Oxide Encapsulated in MOFPA Imaging and PTTActivation under an acidic tumor environment for imaging and ablation.[19]
Manganese Ferrite Nanoparticles (MnFe2O4)MRIMagnetic targeting and ROS-induced cytotoxicity for synergistic therapy.[11]
Gold-Decorated Silicon Nanorods (Au@SiNRs)Infrared ImagingStable over repeated laser cycles, enabling tumor targeting and imaging.[9]
Gold Nanostars (Au nanostars-1 and Au nanostars-2)NIR ImagingHigh NIR absorption with a strong surface-enhanced Raman spectroscopy signal for effective cancer imaging.[59]
Copper Sulfide Nanoparticles on SilicaTetramodal ImagingEnables synergistic photothermal and photodynamic therapy, leading to complete tumor elimination.[45]
Table 2. Therapeutic applications of nanomaterials: innovations in PTT, PDT, and combination therapies.
Table 2. Therapeutic applications of nanomaterials: innovations in PTT, PDT, and combination therapies.
Materials UsedTherapy/Therapies AppliedKey FeaturesRef.
BSA, Gd2O3, IrO2Photothermal Therapy (PTT), Photodynamic Therapy (PDT)Combination therapy[1]
Conjugated polymer, thermosensitive NO DonorPhotothermal Therapy (PTT), Nitric Oxide (NO) ReleaseNO enhances therapy[2]
Gold nanorods, PD-L1 aptamerPhotothermal ImmunotherapyTargets PD-L1[3]
Polyprodrug-modified iron oxide nanoparticlesPhotodynamic Therapy (PDT), ChemotherapySize-changeable, stimuli-responsive[5]
Polydopamine-doxorubicin conjugate nanoparticlesChemotherapy, Photothermal Therapy (PTT)Triple-mode imaging[21]
Ag2Se nanodots on upconversion nanoparticlesPhotothermal Therapy (PTT)Under 808 nm laser[58]
Dual-activatable self-assembled nanotheranosticsPhotodynamic Therapy (PDT)pH/redox-sensitive activation[13]
Gold nanostarsPhotothermal Therapy (PTT)Size-tuned for therapy and imaging[59]
Gd-chelated conjugated polymer nanoparticlesPhotothermal Therapy (PTT)Imaging-guided therapy[77]
Gd and CuS nanoparticles with BSAPhotothermal Therapy (PTT)Biodegradable, immune activation[78]
Gold nanocages with hyaluronic acidPhotodynamic Therapy (PDT), PTT, RadiosensitizerSynergistic therapy[74]
Manganese oxide nanosheets with PDA and ICGPhotodynamic Therapy (PDT), Photothermal Therapy (PTT)Oxygen release to enhance PDT[79]
Table 3. Stimuli-responsive and targeted nanomaterials.
Table 3. Stimuli-responsive and targeted nanomaterials.
Materials UsedStimulus Responsiveness or Targeting StrategyKey FeaturesRef.
Thermosensitive NO donor (BNN6)Heat-responsive decomposition under NIR-II laserControlled NO release[2]
Gold nanodandelions with gelatinAcidic tumor conditions, MMP-triggered aggregationPrecise PTT control[37]
Polypeptide-encapsulated BODIPYpH-sensitive fluorescence activation in acidic lysosomesEnhanced targeting[10]
Polydopamine-doxorubicin conjugate nanoparticlespH-sensitive drug release in tumor microenvironmentSelective tumor accumulation[21]
Chlorin e6 (Ce6)-linked pH and redox-sensitive polymer ligandpH/redox-sensitive charge switch enhances cellular uptakeTargeted PDT within tumor cells[13]
Ferrous ion-doped layered double hydroxide with doxorubicinpH-responsive degradation in acidic tumor environmentsMRI-guided chemo/PTT[64]
iRGD-coated maleimide-poly(ethylene glycol)-poly(lactic acid/glycolic acid)-encapsulated gold nanocagesActive targeting with iRGD peptide, mild PTT triggers drug releaseTime-dependent cell death[86]
Diradicaloid small molecule nanotheranosticHigh NIR absorbance enhances PAI and PTTStrong light-harvesting ability[87]
Graphene oxide-iron oxide nanotheranosticLymphatic mapping via lymphatic vessel travelIntraoperative guidance[88]
Gold nanocages with hyaluronic acidTargets CD44 receptor via hyaluronic acidSynergistic therapy under PA guidance[74]
Gd and CuS nanoparticles with BSABiodegradable with hepatic clearance, immune response activation under NIRHigh photostability[78]
Table 4. Key physicochemical properties of nanomaterials for advanced theranostics.
Table 4. Key physicochemical properties of nanomaterials for advanced theranostics.
Materials UsedPhysicochemical PropertiesRef.
BSA, Gd2O3, IrO2High longitudinal relaxivity (5.2 mM⁻1s⁻1), high photothermal efficiency (66.7%), and catalase-like activity[1]
Conjugated polymer, thermosensitive NO donor (BNN6)Hyperthermia and NO release under single NIR-II laser irradiation[2]
Gold nanorods, PD-L1 aptamerTargeted PA imaging, immune checkpoint inhibition, activation of cytotoxic T cells, and tumor suppression[3]
Gd@graphene carbon nanoparticlesHigh T₁ relaxivity (16.0 × 10⁻3 m⁻1s⁻1), fluorescence, effective renal clearance, and minimal toxicity[8]
Gold nanodandelions with gelatinTumor acidity and MMP-activated, high photothermal efficiency, enhanced PA/PTT imaging, and metastasis control[37]
Polypeptide-encapsulated BODIPYpH-sensitive fluorescence enhancement, high singlet oxygen quantum yield (81.8%), and lysosome targeting[10]
Prussian blue nanoparticles, gold NanoparticlesSynergistic PTT-RT effects, complete tumor suppression, and high biocompatibility[14]
Polydopamine-doxorubicin conjugate nanoparticlesHigh photothermal conversion efficiency, dual stimuli-triggered drug release, and 12.4-fold extended circulation time[21]
Gd-chelated conjugated polymer nanoparticlesTri-modal imaging (PA, NIR-II, MR), high stability, and effective PTT[77]
Gold-palladium cluster nanotheranostic with BSAOxygen-independent ROS generation, strong NIR-II fluorescence and PAI, and enhanced tumor targeting[89]
Diradicaloid small molecule nanotheranostic (DRM)High NIR absorbance, excellent photostability, and effective PAI-guided PTT[87]
Gold nanocages with hyaluronic acidStrong NIR absorbance, effective radiosensitization, PA imaging, and enhanced combination therapy (RT, PDT, PTT)[74]
Table 5. Therapeutic outcomes of advanced nanomaterials in cancer treatment.
Table 5. Therapeutic outcomes of advanced nanomaterials in cancer treatment.
Materials UsedTherapeutic OutcomesRef.
Gold nanorods, PD-L1 aptamerTumor suppression, activation of cytotoxic T cells, enhanced immunotherapy, and a blockade of immune checkpoints through PD-L1 inhibition[3]
Polyprodrug-modified iron oxide nanoparticlesImproved tumor retention, efficient ROS production, and reduced long-term toxicity[5]
Gold nanodandelions with gelatinPrecise PTT control, metastasis control at moderate temperatures, and enhanced imaging[37]
Prussian blue nanoparticles, gold nanoparticlesComplete tumor suppression, synergistic PTT-RT effects, and minimal toxicity[14]
Polydopamine-doxorubicin conjugate nanoparticlesEffective chemotherapy and PTT, selective tumor accumulation, and reduced side effects[21]
Gd-chelated conjugated polymer nanoparticlesSignificant tumor suppression under NIR light, and imaging-guided therapy[77]
Gold-palladium cluster nanotheranostic with BSAEnhanced therapeutic monitoring and effective PDT and catalytic therapy in hypoxic tumors[89]
Diradicaloid small molecule nanotheranostic (DRM)Effective cancer imaging, significant tumor suppression, and strong light-harvesting ability[87]
Ultrasmall SPIO nanoparticles with Sialyl Lewis XAmplified immune response through PTT, enhanced T cell infiltration, and significant tumor inhibition[15]
Gold nanocages with hyaluronic ccidImproved tumor suppression under imaging guidance and synergistic RT and PDT/PTT[74]
Table 6. Biocompatibility and clearance profiles of nanomaterials in theranostics.
Table 6. Biocompatibility and clearance profiles of nanomaterials in theranostics.
Materials UsedBiocompatibility and Clearance ProfilesRef.
Gd@graphene carbon nanoparticlesEffective renal clearance, minimal toxicity, and suitability for clinical applications[8]
Polyprodrug-modified iron oxide nanoparticlesFast elimination post-treatment, high biocompatibility, and reduced long-term toxicity[5]
Gold nanodandelions with gelatinActivated only in the tumor microenvironment, reducing off-target effects, and high biocompatibility[37]
Polypeptide-encapsulated BODIPYMinimal impact on healthy tissues due to pH-sensitive activation, and low background toxicity[10]
Prussian blue nanoparticles, gold nanoparticlesHigh biocompatibility, minimal systemic toxicity, and safe for in vivo applications[14]
Gold-palladium cluster nanotheranostic with BSASafe for clinical applications; oxygen-independent ROS generation minimizes hypoxia-related issues[89]
Ultrasmall SPIO nanoparticles with Sialyl Lewis XRapid systemic clearance, low long-term toxicity, and safe immune activation[15]
Gold nanocages with hyaluronic AcidBiodegradable, minimal toxicity, and suitability for clinical translation[74]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Omidian, H.; Dey Chowdhury, S. Advances in Photothermal and Photodynamic Nanotheranostics for Precision Cancer Treatment. J. Nanotheranostics 2024, 5, 228-252. https://doi.org/10.3390/jnt5040014

AMA Style

Omidian H, Dey Chowdhury S. Advances in Photothermal and Photodynamic Nanotheranostics for Precision Cancer Treatment. Journal of Nanotheranostics. 2024; 5(4):228-252. https://doi.org/10.3390/jnt5040014

Chicago/Turabian Style

Omidian, Hossein, and Sumana Dey Chowdhury. 2024. "Advances in Photothermal and Photodynamic Nanotheranostics for Precision Cancer Treatment" Journal of Nanotheranostics 5, no. 4: 228-252. https://doi.org/10.3390/jnt5040014

APA Style

Omidian, H., & Dey Chowdhury, S. (2024). Advances in Photothermal and Photodynamic Nanotheranostics for Precision Cancer Treatment. Journal of Nanotheranostics, 5(4), 228-252. https://doi.org/10.3390/jnt5040014

Article Metrics

Back to TopTop