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48 pages, 12603 KiB  
Review
Advances in Nanotheranostic Systems for Concurrent Cancer Imaging and Therapy: An Overview of the Last 5 Years
by Anna Małgorzata Lankoff, Malwina Czerwińska and Marcin Kruszewski
Molecules 2024, 29(24), 5985; https://doi.org/10.3390/molecules29245985 - 19 Dec 2024
Viewed by 939
Abstract
The rapid development of nanotechnology during the last two decades has created new opportunities to design and generate more advanced nanotheranostics with diversified capabilities for diagnosis, drug delivery, and treatment response monitoring in a single platform. To date, several approaches have been employed [...] Read more.
The rapid development of nanotechnology during the last two decades has created new opportunities to design and generate more advanced nanotheranostics with diversified capabilities for diagnosis, drug delivery, and treatment response monitoring in a single platform. To date, several approaches have been employed in order to develop nanotheranostics. The purpose of this review is to briefly discuss the key components of nanotheranostic systems, to present the conventional and upcoming imaging and therapeutic modalities that employ nanotheranostic systems, and to evaluate recent progress in the field of cancer nanotheranostic systems in the past five years (2020–2024). Special attention is focused on the design of cancer nanotheranostic systems, their composition, specificity, potential for multimodal imaging and therapy, and in vitro and in vivo characterization. Full article
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<p>The main components of nanotheranostic systems, including a nanoparticle-based carrier, surface modifiers, and biomedical payload.</p>
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<p>Schematic representation of the DOX-TFP-MNPs nanotheranostic system.</p>
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<p>Schematic representation of the Cur/ALN-β-CD-SPIONs nanotheranostic system.</p>
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<p>Schematic representation of the YC-9-MNPs nanotheranostic system.</p>
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<p>Schematic representation of the Fe<sub>3</sub>O<sub>4</sub>-Cy5.5 nanotheranostic system.</p>
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<p>Schematic representation of the Fe<sub>3</sub>O<sub>4</sub>@PCD-Gd/CUR nanotheranostic system.</p>
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<p>Schematic representation of the HA-FeWO<sub>4</sub> NPs nanotheranostic system.</p>
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<p>Schematic representation of the CM-DOX-GMNPs nanotheranostic system.</p>
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<p>Schematic representation of the GNR@PDA nanotheranostic system.</p>
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<p>Schematic representation of the <sup>67</sup>Ga-AuNP-BBN-Pt1 nanotheranostic system.</p>
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<p>Schematic representation of the Au(L-Cys DTPA) (Propargylamine)-AF647 nanotheranostic system.</p>
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<p>Schematic representation of the SPN-I nanotheranostic system.</p>
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<p>Schematic representation of the SPN nanotheranostic system.</p>
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<p>Schematic representation of the HA-HDAPP nanotheranostic system.</p>
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<p>Schematic representation of the [<sup>89</sup>Zr]DFB(25)ACUPA(75) nanotheranostic system.</p>
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<p>Schematic representation of the Gd–PNP nanotheranostic system.</p>
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<p>Schematic representation of the SS<sub>TPTX</sub> nanotheranostic system.</p>
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<p>Schematic representation of the CuNC(Octa) nanotheranostic system.</p>
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<p>Schematic representation of the PB-UMN-CS-ES-FA-NP nanotheranostic system.</p>
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<p>Schematic representation of the DOX@Fe-HMON-Tf nanotheranostic system.</p>
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<p>Schematic representation of MSN@H6L@β-CD@AMPPD nanotheranostics platform.</p>
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<p>Schematic representation of DOX–carbanosilica nanotheranostic system.</p>
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<p>Schematic representation of the FS-DT-Chl-FA-Sn-AX nanotheranostic system.</p>
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<p>Schematic representation of the SSPN nanotheranostic system.</p>
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<p>Schematic representation of the DOX-DSPC-IJA-HBS nanotheranostic system.</p>
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<p>Schematic representation of the DiR-BOA-HPPS-mAb/siRNA nanotheranostic system.</p>
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<p>Schematic representation of the Au<sub>4</sub>Cu<sub>4</sub>/Au<sub>25</sub>@Lip nanotheranostic system.</p>
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<p>Schematic representation of the thermosensitive iTSL-DOX nanotheranostic system.</p>
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<p>Schematic representation of the Gd-Au-DENPs-Nit nanotheranostic system.</p>
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<p>Schematic representation of the SNP<sub>ICG/Ce6</sub> nanoplatform.</p>
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<p>Schematic representation of the PRDCuS@AG nanotheranostic system.</p>
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<p>Schematic representation of the RGD-CuS DENPs/pDNA polyplex nanosystem.</p>
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<p>Schematic representation of the GPCP/miR-21i/ICG nanocomplex.</p>
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<p>Schematic representation of the chalcone–APBA-CD nanotheranostic system.</p>
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<p>Schematic representation of the BA-PHCDs nanotheranostic system.</p>
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<p>Schematic representation of the Ir1-AuSiO2 nanotheranostic system.</p>
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<p>Schematic representation of the NaErF4@ Ti3C2 nanotheranostic system.</p>
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<p>Schematic representation of the Ti<sub>3</sub>C<sub>2</sub> Tx-Pt-PEG 2D nanocomposite.</p>
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<p>Schematic representation of the GO-SPIO-Au-DOX-TD-Alg nanotheranostic system.</p>
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<p>Schematic representation of the CuS-PEI-ICG-FA nanotheranostic system.</p>
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<p>Schematic representation of the GION@RGD nanotheranostic system.</p>
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25 pages, 13479 KiB  
Review
Advances in Photothermal and Photodynamic Nanotheranostics for Precision Cancer Treatment
by Hossein Omidian and Sumana Dey Chowdhury
J. Nanotheranostics 2024, 5(4), 228-252; https://doi.org/10.3390/jnt5040014 - 13 Dec 2024
Viewed by 500
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 [...] Read more.
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. Full article
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<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>
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<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>
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<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>
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20 pages, 1211 KiB  
Review
Nanotheranostics in Breast Cancer Bone Metastasis: Advanced Research Progress and Future Perspectives
by Lin Miao, Yidan Zhu, Hong Chang and Xinfeng Zhang
Pharmaceutics 2024, 16(12), 1491; https://doi.org/10.3390/pharmaceutics16121491 - 21 Nov 2024
Viewed by 628
Abstract
Breast cancer is the leading cause of cancer-related morbidity and mortality among women worldwide, with bone being the most common site of all metastatic breast cancer. Bone metastases are often associated with pain and skeletal-related events (SREs), indicating poor prognosis and poor quality [...] Read more.
Breast cancer is the leading cause of cancer-related morbidity and mortality among women worldwide, with bone being the most common site of all metastatic breast cancer. Bone metastases are often associated with pain and skeletal-related events (SREs), indicating poor prognosis and poor quality of life. Most current therapies for breast cancer bone metastasis primarily serve palliative purposes, focusing on pain management, mitigating the risk of bone-related complications, and inhibiting tumor progression. The emergence of nanodelivery systems offers novel insights and potential solutions for the diagnosis and treatment of breast cancer-related bone metastasis. This article reviews the recent advancements and innovative applications of nanodrug delivery systems in the context of breast cancer bone metastasis and explores future directions in nanotheranostics. Full article
(This article belongs to the Special Issue Micro/Nano Drug Delivery Systems)
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<p>The nanoparticles through the blood–bone marrow barriers pathway (by Figdraw (<a href="https://www.figdraw.com" target="_blank">https://www.figdraw.com</a>)).</p>
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<p>The process of bone metastasis in breast cancer and the mode of action of drug delivery systems (by Figdraw).</p>
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37 pages, 5693 KiB  
Review
Alzheimer’s Disease Pathology and Assistive Nanotheranostic Approaches for Its Therapeutic Interventions
by Anuvab Dey, Subhrojyoti Ghosh, Ramya Lakshmi Rajendran, Tiyasa Bhuniya, Purbasha Das, Bidyabati Bhattacharjee, Sagnik Das, Atharva Anand Mahajan, Anushka Samant, Anand Krishnan, Byeong-Cheol Ahn and Prakash Gangadaran
Int. J. Mol. Sci. 2024, 25(17), 9690; https://doi.org/10.3390/ijms25179690 - 7 Sep 2024
Viewed by 1390
Abstract
Alzheimer’s disease (AD) still prevails and continues to increase indiscriminately throughout the 21st century, and is thus responsible for the depreciating quality of health and associated sectors. AD is a progressive neurodegenerative disorder marked by a significant amassment of beta-amyloid plaques and neurofibrillary [...] Read more.
Alzheimer’s disease (AD) still prevails and continues to increase indiscriminately throughout the 21st century, and is thus responsible for the depreciating quality of health and associated sectors. AD is a progressive neurodegenerative disorder marked by a significant amassment of beta-amyloid plaques and neurofibrillary tangles near the hippocampus, leading to the consequent loss of cognitive abilities. Conventionally, amyloid and tau hypotheses have been established as the most prominent in providing detailed insight into the disease pathogenesis and revealing the associative biomarkers intricately involved in AD progression. Nanotheranostic deliberates rational thought toward designing efficacious nanosystems and strategic endeavors for AD diagnosis and therapeutic implications. The exceeding advancements in this field enable the scientific community to envisage and conceptualize pharmacokinetic monitoring of the drug, sustained and targeted drug delivery responses, fabrication of anti-amyloid therapeutics, and enhanced accumulation of the targeted drug across the blood–brain barrier (BBB), thus giving an optimistic approach towards personalized and precision medicine. Current methods idealized on the design and bioengineering of an array of nanoparticulate systems offer higher affinity towards neurocapillary endothelial cells and the BBB. They have recently attracted intriguing attention to the early diagnostic and therapeutic measures taken to manage the progression of the disease. In this article, we tend to furnish a comprehensive outlook, the detailed mechanism of conventional AD pathogenesis, and new findings. We also summarize the shortcomings in diagnostic, prognostic, and therapeutic approaches undertaken to alleviate AD, thus providing a unique window towards nanotheranostic advancements without disregarding potential drawbacks, side effects, and safety concerns. Full article
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<p>In a healthy brain (<b>A</b>), insulin binding to its receptor activates IRS-1 and PI3K, supporting neuronal health, growth, and cognitive functions. This process also balances blood vessel dilation and constriction to meet metabolic needs. In AD (<b>B</b>), Aβ oligomers disrupt this system by increasing TNF-α and activating stress kinases like JNK, which negatively affects IRS-1 (1). These oligomers also displace insulin receptors (IRs) from the cell surface by the actions of CK2 and CaMKII, relocating them away from areas where they are needed (2). This leads to insulin resistance, decreasing Aβ-degrading enzyme (IDE) levels (3), thus reducing Aβ clearance. The impaired insulin signaling escalates GSK-3β activity (4), promoting abnormal tau phosphorylation and damaging neuronal functions and cognitive abilities (5). Furthermore, this dysfunction disrupts vascular regulation (6), reducing nitric oxide (NO) production, decreasing cerebral blood flow, and increasing inflammation and oxidative stress (reprinted with permission from ref [<a href="#B17-ijms-25-09690" class="html-bibr">17</a>] with CC BY license Copyright© 2015 Bedse, Di Domenico, Serviddio and Cassano). CaMKII—Calcium/calmodulin-dependent protein kinase II; CK2—Casein kinase 2; eNOS—Endothelial nitric oxide synthase; ET—Endothelin; GSK-3β—Glycogen synthase kinase-3 beta; IDE—Insulin-degrading enzyme; IRS-1—Insulin receptor substrate 1; JNK—c-Jun N-terminal kinase; NO—Nitric oxide; PI3K—Phosphoinositide 3-kinase; TNF-α—Tumor necrosis factor-alpha; and TNFR—Tumor necrosis factor receptor.</p>
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<p>Pathways leading to AD because of oxidative stress and protein misfolding. This diagram illustrates the cascade of events starting with oxidative stress, characterized by the overproduction of ROS. This triggers neuroinflammation and activates microglia, leading to mitochondrial dysfunction (as indicated by decreased ATP levels). The process involves the increased activity of GSK-3β and decreased activity of PP2A, contributing to the hyperphosphorylation of tau proteins. Consequently, there is an accumulation of NFTs and Aβ plaques, which are hallmarks of AD. This sequence of events leads to proteasomal malfunction, further exacerbating protein misfolding and ultimately causing neuronal apoptosis. These interconnected pathways culminate in the development and progression of AD (created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>Diagram illustrating the routes for autophagy and mitophagy. (<b>A</b>) In response to nutrient or energy stress, AMPK is activated, and mTORC1 is suppressed, which increases ULK1 complex activity and stimulates the creation of the VPS34 and ATG5-12-16L complexes, which, in turn, stimulates the production of phagophores and autophagosomes. (<b>B</b>) Depolarization of the mitochondria stabilizes PINK1 and stimulates PINK/Parkin signaling, which increases OMM’s phospho-ubiquitin conjugation. Mitophagy receptors like OPTN and NDP52 identify the polyubiquitin chain, which promotes mitophagosome formation (created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>Diagram illustrating how antibodies specific to tau and Aβ work near each other; along with streptavidin-coated gold nanoparticles (S-AuNP) and biotin-coated Aβ-antibody interaction, we can diagnose AD (created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>The role of nanoparticles in overcoming the BBB for efficient delivery of therapeutic moieties to treat AD. (<b>A</b>) Image of human brain. (<b>B</b>) Components of the BBB. (<b>C</b>) Functionalized nanoparticles (NPs) for imaging and targeted drug delivery to the AD brain. (<b>D</b>) Different pathways of transport (a–e) across the BBB utilized by functionalized NPs. (a) Transport of NPs through cellular transport proteins; (b) transport of NPs through tight junctions; (c) transport of NPs via receptor-mediated transcytosis; (d) transport of NPs via transcellular pathway following diffusion, specifically adopted by gold NPs; (e) transport of cationic NPs and liposomes via adsorption-mediated transcytosis. (<b>E</b>) Effect of functionalized NPs in treating AD via the degradation of tau aggregates and efflux of Aβ fibrils after becoming solubilized by the NPs (reprinted with permission from ref [<a href="#B129-ijms-25-09690" class="html-bibr">129</a>] with CC BY 4.0 license Copyright© 2021 Khan, Mir, Ngowi, Zafar, Khakwani, Khattak, Zhai, Jiang, Zheng, Duan, Wei, Wu, and Ji).</p>
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<p>Schematic representation of a biosensor device for detecting biomarkers in a sample. The device consists of a bioreceptor component where specific biomarkers from the sample bind to the surface. Various nanomaterials such as carbon nanotubes, quantum dots, graphene oxide, metallic nanoparticles, and magnetic nanoparticles are used to enhance the specificity and sensitivity of the bioreceptor. In contact with the bioreceptor, the transducer element converts the biochemical signal into an electrical signal through either optical or electrochemical means. This signal is then relayed to the electronics component, which processes the signal for subsequent detection and quantification of the analyte (created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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67 pages, 4706 KiB  
Review
Nanoformulations in Pharmaceutical and Biomedical Applications: Green Perspectives
by Sanja Petrovic, Bogdan Bita and Marcela-Elisabeta Barbinta-Patrascu
Int. J. Mol. Sci. 2024, 25(11), 5842; https://doi.org/10.3390/ijms25115842 - 27 May 2024
Cited by 7 | Viewed by 4010
Abstract
This study provides a brief discussion of the major nanopharmaceuticals formulations as well as the impact of nanotechnology on the future of pharmaceuticals. Effective and eco-friendly strategies of biofabrication are also highlighted. Modern approaches to designing pharmaceutical nanoformulations (e.g., 3D printing, Phyto-Nanotechnology, Biomimetics/Bioinspiration, [...] Read more.
This study provides a brief discussion of the major nanopharmaceuticals formulations as well as the impact of nanotechnology on the future of pharmaceuticals. Effective and eco-friendly strategies of biofabrication are also highlighted. Modern approaches to designing pharmaceutical nanoformulations (e.g., 3D printing, Phyto-Nanotechnology, Biomimetics/Bioinspiration, etc.) are outlined. This paper discusses the need to use natural resources for the “green” design of new nanoformulations with therapeutic efficiency. Nanopharmaceuticals research is still in its early stages, and the preparation of nanomaterials must be carefully considered. Therefore, safety and long-term effects of pharmaceutical nanoformulations must not be overlooked. The testing of nanopharmaceuticals represents an essential point in their further applications. Vegetal scaffolds obtained by decellularizing plant leaves represent a valuable, bioinspired model for nanopharmaceutical testing that avoids using animals. Nanoformulations are critical in various fields, especially in pharmacy, medicine, agriculture, and material science, due to their unique properties and advantages over conventional formulations that allows improved solubility, bioavailability, targeted drug delivery, controlled release, and reduced toxicity. Nanopharmaceuticals have transitioned from experimental stages to being a vital component of clinical practice, significantly improving outcomes in medical fields for cancer treatment, infectious diseases, neurological disorders, personalized medicine, and advanced diagnostics. Here are the key points highlighting their importance. The significant challenges, opportunities, and future directions are mentioned in the final section. Full article
(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)
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<p>Illustration of wide use of nanopharmaceuticals. Figure was created with ChemOfficeUltra 2007 and with PowerPoint Version 2307.</p>
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<p>Schematic representation of liposome preparation by thin film hydration method. Figure was created with ChemOfficeUltra 2007 and with PowerPoint.</p>
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<p>Schematic representation of “green” synthesis of MNPs/MONPs. Figure was created with Chemix (<a href="https://chemix.org/" target="_blank">https://chemix.org/</a>, accessed on 21 March 2024) and with PowerPoint and Paint 3D version 1.0.46.0.</p>
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<p>SEM image and the antioxidant activity (AA%) of AuAgClZnONPs phyto-generated from burdock extract (BE) (Adapted upon [<a href="#B107-ijms-25-05842" class="html-bibr">107</a>]).</p>
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<p>Illustration of a Quantum dot architecture. Figure was created with PowerPoint.</p>
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<p>Schematic representation of symbiotic relationship in microbiome. Figure was created Microsoft PowerPoint.</p>
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<p>Schematic representation of the structure of nanocapsules (adapted upon [<a href="#B202-ijms-25-05842" class="html-bibr">202</a>]).</p>
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<p>Lower-Sized Chitosan Nanocapsules for Transcutaneous Antigen Delivery (adapted from [<a href="#B205-ijms-25-05842" class="html-bibr">205</a>]).</p>
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<p>The 3D printing techniques commonly used in the fabrication of personalized medicines (abbreviations: fuse deposition modeling, FDM; direct powder extrusion, DPE; semisolid extrusion, SSE; pressure-assisted microsyringes, PAM; stereolithography, SLA; selective laser sintering, SLS) [<a href="#B255-ijms-25-05842" class="html-bibr">255</a>].</p>
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<p>The workflow of 3D printing of dapagliflozin-containing self-nanoemulsifying tablets [<a href="#B256-ijms-25-05842" class="html-bibr">256</a>].</p>
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<p>Different targeting ligands used in targeted drug delivery [<a href="#B289-ijms-25-05842" class="html-bibr">289</a>].</p>
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<p>Schematic representation of the drug-releasing mechanisms of different types of drug nanocarriers [<a href="#B301-ijms-25-05842" class="html-bibr">301</a>].</p>
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<p>Illustration of intracellular delivery of plasmid DNA to the nucleus of HeLa cancer cell using ROS-responsive polymer-based LWM PEI and thioacetal-linker units (adapted from [<a href="#B308-ijms-25-05842" class="html-bibr">308</a>]).</p>
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<p>Morphology of MCF-7 breast cancer cells at 12 h post-Hyp-AuNP compound PDT treatment [<a href="#B343-ijms-25-05842" class="html-bibr">343</a>].</p>
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<p>Photographs of the growth of <span class="html-italic">Escherichia coli</span> incubated with sterilized water (control) and with three types of composites molybdenum disulfide (MoS<sub>2</sub>)@gold nanorods (AuNRs) on LB agar plates after NIR laser, visible light, or both NIR laser and visible light irradiation [<a href="#B344-ijms-25-05842" class="html-bibr">344</a>].</p>
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<p>Nanotheranostics: metallic, polymeric, and lipid-based nanosystems for cancer management [<a href="#B366-ijms-25-05842" class="html-bibr">366</a>].</p>
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<p><span class="html-italic">In vitro</span> cellular toxicity of TT-RBC-NPs in three-dimensional (3D) spheroids. (<b>a</b>) <span class="html-italic">In vitro</span> live/dead cell imaging of tumor spheroid, untreated and treated with free DOX, RBC-NPs, and TTRBC-NPs (equivalent of 1 µg/mL DOX) for a period of 4, 24, and 48 h. Two-color fluorescence, live (green channel) and dead (red channel), enables evaluation of live and dead cells to determine cell viability. Scale bar = 200 µm. (<b>b</b>) <span class="html-italic">In vitro</span> cytotoxicity study using CellTiter-Glo<sup>®</sup> 3D cell assay of untreated, free DOX, RBC-NPs, and TT-RBC-NPs against 3D MCF-7 spheroids. Results represent mean ± SD (<span class="html-italic">n</span> = 3). * the significance between Untreated, Free DOX, RBC-NPs, and TT-RBC-NPs at 48 h incubation (<span class="html-italic">p</span> &lt; 0.05). ** the significance between 4 h and 48 h incubation of TT-RBC-N [<a href="#B367-ijms-25-05842" class="html-bibr">367</a>].</p>
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<p>Schematic representation of the main challenges regarding nanopharmaceuticals. Figure was created Microsoft PowerPoint.</p>
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25 pages, 2201 KiB  
Review
Revolution in Cancer Treatment: How Are Intelligently Designed Nanostructures Changing the Game?
by Désirée Gül, Burcu Önal Acet, Qiang Lu, Roland H. Stauber, Mehmet Odabaşı and Ömür Acet
Int. J. Mol. Sci. 2024, 25(10), 5171; https://doi.org/10.3390/ijms25105171 - 9 May 2024
Cited by 4 | Viewed by 1646
Abstract
Nanoparticles (NPs) are extremely important tools to overcome the limitations imposed by therapeutic agents and effectively overcome biological barriers. Smart designed/tuned nanostructures can be extremely effective for cancer treatment. The selection and design of nanostructures and the adjustment of size and surface properties [...] Read more.
Nanoparticles (NPs) are extremely important tools to overcome the limitations imposed by therapeutic agents and effectively overcome biological barriers. Smart designed/tuned nanostructures can be extremely effective for cancer treatment. The selection and design of nanostructures and the adjustment of size and surface properties are extremely important, especially for some precision treatments and drug delivery (DD). By designing specific methods, an important era can be opened in the biomedical field for personalized and precise treatment. Here, we focus on advances in the selection and design of nanostructures, as well as on how the structure and shape, size, charge, and surface properties of nanostructures in biological fluids (BFs) can be affected. We discussed the applications of specialized nanostructures in the therapy of head and neck cancer (HNC), which is a difficult and aggressive type of cancer to treat, to give an impetus for novel treatment approaches in this field. We also comprehensively touched on the shortcomings, current trends, and future perspectives when using nanostructures in the treatment of cancer. Full article
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<p>Exploring nanoparticles (NPs) for cancer therapy. NPs are utilized for various purposes in cancer treatment, including tumor targeting, drug delivery, photo-/radio-/chemo-nanotherapy—where NPs act as active agents, not just as carriers—as well as imaging and diagnosis. Created with BioRender.com.</p>
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<p>Surface modifications of nanoparticles for cancer therapy. Surface modifications of NPs aiming at the improvement of biocompatibility, targeting ability, and therapeutic efficacy can be classified into four groups: (1) Biomimetic coatings, which are mainly made of different (bio)membranes mimicking a biological identity. (2) Targeting ligands: NPs are conjugated with targeting ligands such as antibodies, peptides, or aptamers to enhance specific binding to cancer cells or tumor vasculature. (3) Responsive coatings, which include different polymers that are sensitive towards an acidic pH or enzyme that is present in the tumor microenvironment, or external heat, resulting in controlled drug release. (4) Polyethylene glycol (PEG)ylation of NPs improves their stability, reduces clearance by the immune system, and prolongs circulation time in the bloodstream. Created with BioRender.com.</p>
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<p>Studies analyzing nanostructured tools for head and neck cancer treatment are significantly underrepresented among all studies dealing with NP-based cancer applications. Blue: number of total publications by publication year (Pubmed search query: “cancer [title] treatment nanostructure nanoparticle NOT review”; accessed on 1 March 2024). Red: number of HNC-related publications by publication year (Pubmed search query: “head and neck cancer [title] treatment nanostructure nanoparticle NOT review”; accessed on 1 March 2024).</p>
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<p>Advantages of nanoparticles (NPs) in cancer treatment. NPs commonly used for cancer therapy and diagnosis are grouped according to their chemical characteristics (liposomal, inorganic, and polymeric). NPs execute multiple effects, including improved targeted delivery, and bioavailability, controlled release, reduced toxicity, and multifunctionality (e.g., for bioimaging). ‘Minus’ indicate decrease, ‘plus’ increase/improvement by NP-based application. Created with BioRender.com.</p>
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<p>Targeting of cancer cells by nanotechnical delivery platforms. Examples for NPs used for DD are shown in (<b>A</b>). Loaded drugs can be delivered by EPR-based, passive targeting (<b>B</b>) or active targeting (<b>C</b>). Smart NPs allow for stimuli–response drug release, triggered by external or internal factors, such as pH or temperature. Created with BioRender.com.</p>
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<p>Suggested optimal physicochemical properties of nanoparticles used for cancer therapy. The physicochemical properties of NPs play a crucial role in their efficiency for therapeutic applications. Some of the key advantageous properties (marked by yellow arrow) include small size range, neutral or slightly negative surface charge, rod- or filamentous shape [<a href="#B152-ijms-25-05171" class="html-bibr">152</a>], targeted surface functionalization and coating (e.g., PEG), efficient encapsulation and controlled release of drug cargo, and high biodegradability and compatibility to minimize toxicity. Created with BioRender.com.</p>
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27 pages, 3358 KiB  
Review
A Nanorobotics-Based Approach of Breast Cancer in the Nanotechnology Era
by Anca-Narcisa Neagu, Taniya Jayaweera, Krishan Weraduwage and Costel C. Darie
Int. J. Mol. Sci. 2024, 25(9), 4981; https://doi.org/10.3390/ijms25094981 - 2 May 2024
Viewed by 3246
Abstract
We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating in nanorobots, have demonstrated ingenious applications in biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem of BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance [...] Read more.
We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating in nanorobots, have demonstrated ingenious applications in biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem of BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance to classic onco-therapies and real-time monitoring of tumors, nanorobots are designed to perform multiple tasks at a small scale, even at the organelles or molecular level. Over the last few years, most nanorobots have been bioengineered as biomimetic and biocompatible nano(bio)structures, resembling different organisms and cells, such as urchin, spider, octopus, fish, spermatozoon, flagellar bacterium or helicoidal cyanobacterium. In this review, readers will be able to deepen their knowledge of the structure, behavior and role of several types of nanorobots, among other nanomaterials, in BC theranostics. We summarized here the characteristics of many functionalized nanodevices designed to counteract the main neoplastic hallmark features of BC, from sustaining proliferation and evading anti-growth signaling and resisting programmed cell death to inducing angiogenesis, activating invasion and metastasis, preventing genomic instability, avoiding immune destruction and deregulating autophagy. Most of these nanorobots function as targeted and self-propelled smart nano-carriers or nano-drug delivery systems (nano-DDSs), enhancing the efficiency and safety of chemo-, radio- or photodynamic therapy, or the current imagistic techniques used in BC diagnosis. Most of these nanorobots have been tested in vitro, using various BC cell lines, as well as in vivo, mainly based on mice models. We are still waiting for nanorobots that are low-cost, as well as for a wider transition of these favorable effects from laboratory to clinical practice. Full article
(This article belongs to the Special Issue The Interplay among Biomolecules and Nanomaterials)
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<p>Diversity and function of nanorobots in BC theranostics.</p>
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<p>BC hallmarks targeted by nanorobots.</p>
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<p>Anti-tumor functions of nanorobots at primary site of BC.</p>
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<p>Anti-metastatic functions of nanorobots.</p>
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<p>Theranostic roles of nanomaterials against BC.</p>
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35 pages, 4279 KiB  
Review
Nano-Innovations in Cancer Therapy: The Unparalleled Potential of MXene Conjugates
by Sanjay Kulkarni, Soji Soman, Prerana D. Navti, Amrita Arup Roy, Ajinkya Nitin Nikam, P. Vineeth, Jahnavi Kulkarni, Krishnaraj Somayaji Shirur, Abhijeet Pandey, Sajan D. George and Srinivas Mutalik
Materials 2024, 17(6), 1423; https://doi.org/10.3390/ma17061423 - 20 Mar 2024
Cited by 4 | Viewed by 2554
Abstract
MXenes are two-dimensional transition metal carbides, nitrides, and carbonitrides that have become important materials in nanotechnology because of their remarkable mechanical, electrical, and thermal characteristics. This review emphasizes how crucial MXene conjugates are for several biomedical applications, especially in the field of cancer. [...] Read more.
MXenes are two-dimensional transition metal carbides, nitrides, and carbonitrides that have become important materials in nanotechnology because of their remarkable mechanical, electrical, and thermal characteristics. This review emphasizes how crucial MXene conjugates are for several biomedical applications, especially in the field of cancer. These two-dimensional (2D) nanoconjugates with photothermal, chemotherapeutic, and photodynamic activities have demonstrated promise for highly effective and noninvasive anticancer therapy. MXene conjugates, with their distinctive optical capabilities, have been employed for bioimaging and biosensing, and their excellent light-to-heat conversion efficiency makes them perfect biocompatible and notably proficient nanoscale agents for photothermal applications. The synthesis and characterization of MXenes provide a framework for an in-depth understanding of various fabrication techniques and their importance in the customized formation of MXene conjugates. The following sections explore MXene-based conjugates for nanotheranostics and demonstrate their enormous potential for biomedical applications. Nanoconjugates, such as polymers, metals, graphene, hydrogels, biomimetics, quantum dots, and radio conjugates, exhibit unique properties that can be used for various therapeutic and diagnostic applications in the field of cancer nanotheranostics. An additional layer of understanding into the safety concerns of MXene nanoconjugates is provided by detailing their toxicity viewpoints. Furthermore, the review concludes by addressing the opportunities and challenges in the clinical translation of MXene-based nanoconjugates, emphasizing their potential in real-world medical practices. Full article
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<p>General element composition of MAX phase and MXene: M: early transition metal; A: Group A element; X: C and/or N; Tx: surface functional group. Reproduced with permission from [<a href="#B10-materials-17-01423" class="html-bibr">10</a>]. Copyright © 2021, Springer Nature.</p>
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<p>Schematic illustration showing the etching and solvothermal synthesis of MXenes.</p>
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<p>Diagrammatic illustration of the preparation of 2D biodegradable Nb<sub>2</sub>C modified with PVP for in vivo photothermal tumor ablation.</p>
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<p>Pictorial representation of Ti<sub>3</sub>C<sub>2</sub>@Au synthesis, PEGylation, and in vivo PA/CT dual-modal imaging-guided photothermal therapy in combination with radiotherapy.</p>
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<p>Schematic illustration of the potential of MXene–hydrogel conjugates for cancer treatment. Reproduced with permission from [<a href="#B125-materials-17-01423" class="html-bibr">125</a>].</p>
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<p>Overview of cell membrane coating on NPs. Reproduced with permission from [<a href="#B129-materials-17-01423" class="html-bibr">129</a>].</p>
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<p>Pictorial illustration of (<b>A</b>) the preparation of biomimetic plasmonic assemblies, (<b>B</b>) catalytic activity, and (<b>C</b>) therapeutic hypothesis. Reproduced with permission from [<a href="#B107-materials-17-01423" class="html-bibr">107</a>].</p>
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<p>Applications of MXene-QD conjugates. (<b>a</b>) Photothermal images of 4T1 tumor-bearing BALB/c mice administered MXene@EGCG (illumination: 808 nm laser) and (<b>b</b>) the temperature increase curves of the tumors. (<b>c</b>) Western blots showing HSP70 and HSP90 expression in tumor cells from mice. (<b>d</b>) Relative expression of HSPs. Fluorescence emission spectra of (<b>e</b>) aptamer-CGQDs with and without FL-V<sub>2</sub>CT<sub>x</sub>, (<b>f</b>) the aptasensor with the addition of PSA, and (<b>g</b>) the ΔF of the aptasensor for PSA, CEA, CA125, AFP, BSA, and HSA. (<b>a</b>–<b>d</b>) Adapted with permission from [<a href="#B136-materials-17-01423" class="html-bibr">136</a>] and (<b>e</b>–<b>g</b>) adapted with permission from [<a href="#B137-materials-17-01423" class="html-bibr">137</a>].</p>
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<p>The concept of “hospital-on-a-chip” from the MXene-based microneedle system and its versatile applications. Reproduced with permission from [<a href="#B158-materials-17-01423" class="html-bibr">158</a>]. Copyright 2021, American Chemical Society.</p>
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12 pages, 2991 KiB  
Article
The Down-Shifting Luminescence of Rare-Earth Nanoparticles for Multimodal Imaging and Photothermal Therapy of Breast Cancer
by Tingting Gao, Siqi Gao, Yaling Li, Ruijing Zhang and Honglin Dong
Biology 2024, 13(3), 156; https://doi.org/10.3390/biology13030156 - 28 Feb 2024
Viewed by 2061
Abstract
Nanotheranostic agents capable of simultaneously enabling real-time tracking and precise treatment at tumor sites play an increasingly pivotal role in the field of medicine. In this article, we report a novel near-infrared-II window (NIR-II) emitting downconversion rare-earth nanoparticles (RENPs) to improve image-guided therapy [...] Read more.
Nanotheranostic agents capable of simultaneously enabling real-time tracking and precise treatment at tumor sites play an increasingly pivotal role in the field of medicine. In this article, we report a novel near-infrared-II window (NIR-II) emitting downconversion rare-earth nanoparticles (RENPs) to improve image-guided therapy for breast cancer. The developed α-NaErF4@NaYF4 nanoparticles (α-Er NPs) have a diameter of approximately 24.1 nm and exhibit superior biocompatibility and negligible toxicity. RENPs exhibit superior imaging quality and photothermal conversion efficiency in the NIR-II range compared to clinically approved indocyanine green (ICG). Under 808 nm laser irradiation, the α-Er NPs achieve significant tumor imaging performance and photothermal effects in vivo in a mouse model of breast cancer. Simultaneously, it combines X-ray computed tomography (CT) and ultrasound (US) tri-modal imaging to guide therapy for cancer. The integration of NIR-II imaging technology and RENPs establishes a promising foundation for future medical applications. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Molecular Imaging of Cancer)
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<p>α-Er NPs NIR-II imaging of blood vessels and capillary phantom. (<b>a</b>) Schematic of the core–shell structured α-Er nanoparticles. (<b>b</b>) Intensity images of capillaries containing ICG and α-Er NPs. (<b>c</b>) NIR-II image of mouse abdominal vessels with different NIR-II long-pass filters on an InGaAs camera. (<b>d</b>) Fluorescence cross-sectional intensity distribution of abdominal vessels in the NIR-II window (white dotted line in (<b>c</b>)), and the peak pointed by the red arrow in the curve is the location of the blood vessel.</p>
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<p>Pharmacokinetics and cytotoxicity assay of α-Er NPs. (<b>a</b>) Representative examples of whole-body imaging at different time points of intravenous injection of α-Er NPs. (<b>b</b>) Fluorescence images of α-Er NPs in epidermal tumor of the nude mice and the corresponding harvest organs (left to right and to bottom: heart, liver, spleen, lung, kidney, stomach, and intestine). (<b>c</b>) Representative H&amp;E pathological sections of vital organs, including heart, liver, spleen, lung, kidney, lung, and stomach harvested from the mice after being administered with α-Er NPs post-injection. No abnormal lesion or injury was observed in the histological examination of these organs. Scale bar: 50 μm. (<b>d</b>) CCK-8 assay of MCF-7 cells demonstrated no obvious cytotoxicity after 24 h of incubation with diverse concentrations of the α-Er NPs. The concentration gradients were 0, 2, 4, 8, 16, 32, 62.5, 125, and 250 μg/mL, respectively.</p>
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<p>NIR-II/CT/US imaging and PTT for tumor. (<b>a</b>–<b>d</b>) White light and NIR-II/CT/US images of α-Er NPs were captured (Dotted orange circles indicate tumor). (<b>e</b>) Thermal images of mice and the (<b>f</b>) corresponding tumor temperature changes under an 808 nm laser irradiation (1.5 W cm<sup>−2</sup>) for 5 min after the local injection of the agent for 24 h. (<b>g</b>) The picture shows tumors extracted from the different treatment times. (<b>h</b>) The tumor volume ratio of mice at different treatment times.</p>
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33 pages, 4792 KiB  
Review
Bimetallic Coordination Polymers: Synthesis and Applications in Biosensing and Biomedicine
by Yanping Sun, Jianxin Ma, Faisal Ahmad, Yelan Xiao, Jingyang Guan, Tong Shu and Xueji Zhang
Biosensors 2024, 14(3), 117; https://doi.org/10.3390/bios14030117 - 22 Feb 2024
Cited by 3 | Viewed by 3089
Abstract
Bimetallic coordination polymers (CPs) have two different metal ions as connecting nodes in their polymer structure. The synthesis methods of bimetallic CPs are mainly categorized into the one-pot method and post-synthesis modifications according to various needs. Compared with monometallic CPs, bimetallic CPs have [...] Read more.
Bimetallic coordination polymers (CPs) have two different metal ions as connecting nodes in their polymer structure. The synthesis methods of bimetallic CPs are mainly categorized into the one-pot method and post-synthesis modifications according to various needs. Compared with monometallic CPs, bimetallic CPs have synergistic effects and excellent properties, such as higher gas adsorption rate, more efficient catalytic properties, stronger luminescent properties, and more stable loading platforms, which have been widely applied in the fields of gas adsorption, catalysis, energy storage as well as conversion, and biosensing. In recent years, the study of bimetallic CPs synergized with cancer drugs and functional nanomaterials for the therapy of cancer has increasingly attracted the attention of scientists. This review presents the research progress of bimetallic CPs in biosensing and biomedicine in the last five years and provides a perspective for their future development. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Electrochemical Biosensing Application)
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<p>Schematic diagram of the constituent elements of bimetallic CPs and their applications in biosensing and biomedicine.</p>
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<p>One-pot methods for bimetallic CP synthesis. (<b>A</b>) self-assembly methods, (<b>B</b>) metal-ligand methods and post-synthesis modifications, (<b>C</b>) ion-exchange methods, (<b>D</b>) seed methods.</p>
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<p>(<b>A</b>) Schematic illustration of fabrication of Ag/Zn-ZIF-8 and its direct utilization for the detection of Fe<sup>3+</sup> and Cu<sup>2+</sup>. (<b>B</b>) Fluorescence properties of Ag/Zn-ZIF-8 (1:1) toward various cations in DMF solution (λ<sub>ex</sub> = 280 nm). Reproduced with permission from Ref. [<a href="#B84-biosensors-14-00117" class="html-bibr">84</a>]. Copyright 2022, Elsevier.</p>
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<p>(<b>A</b>) Schematic illustration for the preparation of vertical NiCo-MOF nanosheets array. (<b>B</b>) TEM image of vertical NiCo-MOF nanosheets. (<b>C</b>) Amperometric response calibration curve for glucose detection by the constructed electrode. Reproduced with permission from Ref. [<a href="#B102-biosensors-14-00117" class="html-bibr">102</a>]. Copyright 2019, Elsevier.</p>
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<p>(<b>A</b>) Schematic illustration of the fabrication process for FP/Au@NiCo-MOF. (<b>B</b>) Mechanism for constructing a wedge-shaped DNA Walker for rapid and sensitive detection of methylated target DNA. (<b>C</b>) Effect of incubation time on the responses of the traditional DNA walker (red line) and this wedged DNA walker (blue line). (<b>D</b>) Linear relationship between the current values and the logarithmic concentration of methylated DNA (from 0.5 fM to 5 nM). (<b>E</b>) Current responses of human serum samples containing (a) 0 fM, (b) 10 fM, (c) 500 fM, (d) 50 pM, and (e) 5 nM. Reproduced with permission from Ref. [<a href="#B125-biosensors-14-00117" class="html-bibr">125</a>]. Copyright 2023, American Chemical Society.</p>
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<p>(<b>A</b>) Schematic illustration of the preparation of Apt/AuNPs/CoNi-MOF/GCE electrochemical sensor and its voltammetric response toward ENR. (<b>B</b>) Effect of different concentrations of ENR on ΔR<sub>ct</sub>. Inset: the calibration curves. (<b>C</b>) Peak current values of the aptasensor for interferences (10 μg·mL<sup>−1</sup>), ENR (100 ng·mL<sup>−1</sup>), and their mixture (100 ng·mL<sup>−1</sup>). Reproduced with permission from Ref. [<a href="#B150-biosensors-14-00117" class="html-bibr">150</a>]. Copyright 2022, Elsevier.</p>
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<p>(<b>A</b>) Scheme for the synthesis of HMOS@ZC. (<b>B</b>) Schematic for Pt@HMOS without bimetallic MOF gating and Pt-based drugs release profiles of Pt@HMOS at different pH values. (<b>C</b>) Fluorescence images of Calcein AM (green, live cells) and PI (red, dead cells) co-stained A549 cells treated by different formulations for 24 h. (<b>D</b>) In vivo fluorescence images of A549-tumor-bearing mice and (<b>E</b>) quantitative mean fluorescence intensity analysis of tumors at different time points post i.v. injection of free ICG and ICG@HMOS@ZC. (“****” represents that the two groups of data are very different statistically) Reproduced with permission from Ref. [<a href="#B166-biosensors-14-00117" class="html-bibr">166</a>]. Copyright 2022, Wiley Online Library.</p>
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<p>(<b>A</b>) Schematic illustration of the fabrication of Mn/Zr-MOF-shY1-CM. (<b>B</b>) Schematic representation of Mn/Zr-MOF-shY1-CM-induced immune response cascades. (<b>C</b>) QRT-PCR analysis of <span class="html-italic">Cxcl10</span> and <span class="html-italic">Ifnb1</span> expression in BMDCs. (“***” represents a statistically significant difference between the data, ns = not statistically) (<b>D</b>) In situ immune nodule measurement (n = 4). Reproduced with permission from Ref. [<a href="#B170-biosensors-14-00117" class="html-bibr">170</a>]. Copyright 2024, Elsevier.</p>
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<p>(<b>A</b>) Schematic illustration of Co-Fc@GOx as a cascade enzymatic/Fenton reaction platform for promoted •OH induction and enhanced therapeutic effects on cancer cells. Reproduced with permission from Ref. [<a href="#B174-biosensors-14-00117" class="html-bibr">174</a>]. Copyright 2020, Wiley Online Library. (<b>B</b>) Schematic illustration of a smart DNAzyme@Cu/ZIF-8 nanoplatform for the synergistic chemo-gene therapy. Reproduced with permission from Ref. [<a href="#B175-biosensors-14-00117" class="html-bibr">175</a>]. Copyright 2021, Wiley Online Library.</p>
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<p>Schematic illustration for bio-functional Au@MnRu-MOF triggered enhancement of radiotherapy. Reproduced with permission from Ref. [<a href="#B181-biosensors-14-00117" class="html-bibr">181</a>]. Copyright 2023, Wiley Online Library.</p>
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<p>Schematic illustration of the successive fabrication of the AFMMB with DNA demethylation and RNA hypermethylation activities for enhancing antitumor immunity. Reproduced with permission from Ref. [<a href="#B184-biosensors-14-00117" class="html-bibr">184</a>]. Copyright 2023, Wiley Online Library.</p>
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16 pages, 3972 KiB  
Article
Graphene Oxide Chemical Refining Screening to Improve Blood Compatibility of Graphene-Based Nanomaterials
by Fabio Pieretti, Alessandro Moretto, Emanuele Papini and Regina Tavano
J. Nanotheranostics 2024, 5(1), 13-28; https://doi.org/10.3390/jnt5010002 - 20 Feb 2024
Viewed by 1643
Abstract
Graphene oxide (GO) nanoparticles, due to their favorable water solubility, compared to graphene (GA), are a hot research topic in biomedical and pharmaceutical research. However, GO clinical translation may be complicated by its high surface/volume ratio enhancing the interaction with human blood components. [...] Read more.
Graphene oxide (GO) nanoparticles, due to their favorable water solubility, compared to graphene (GA), are a hot research topic in biomedical and pharmaceutical research. However, GO clinical translation may be complicated by its high surface/volume ratio enhancing the interaction with human blood components. In fact, GO’s bi-dimensional nature and strong negative charge may lead to severe biological effects, such as thrombogenicity and immune cell activation. This study explores the impact of further GO surface chemical modulation on major adverse effects: blood plasma coagulation and hemolysis. To this aim, we refined GO nanoparticles by fine-tuned reduction chemistry, esterification and introduction of negative or positive charges. With this approach, we were able to mitigate plasma coagulation and hemolysis at variable degrees and to identify GO derivatives with improved biocompatibility. This opens the door to the progress of graphene-based nanotheranostic applications. Full article
(This article belongs to the Special Issue Carbon Nanomaterials as Nano-Theranostic Tools in Disease Treatment)
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<p>(<b>A</b>) Raman spectra of GO. (<b>B</b>) XPS spectra of GO in the C1s range (purple line) and a multipeak analysis for the carbon 1s (orange line). Green line was used to fit baseline. (<b>C</b>) TEM image of the GO showing aggregates (left), stacked flakes (centre) and single flakes (right).</p>
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<p>(<b>A</b>) UV spectra of reduced GO and rGO samples, obtained at a concentration of 0.05 mg/mL and pH 10. (<b>B</b>) Solid state FT-IR spectra of GO and rGO samples.</p>
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<p>(<b>A</b>) Comparison of UV-Vis spectra of GO and eGO taken, respectively, at the concentrations 0.025 mg/m. (<b>B</b>) comparison of solid-state FT-IR spectra of GO and eGO.</p>
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<p>TEM images of cysGO, met-cysGO and met-cys-e-GO.</p>
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<p>Hemolytic activity for GO and its selected reduced and functionalized derivatives at the concentrations of 2.5 μg/mL and 25 μg/mL, after 18 (left panels) and 24 h (right panels)-incubation with RBCs. Each data point is presented as mean ± absolute error (<span class="html-italic">n</span> = 2). Data are expressed as % of total hemolysis induced by pure distilled water (100% release).</p>
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<p>Hemolytic activity in HS and saline solution for GO and its selected reduced and functionalized derivatives at the concentration of 2.5 μg/mL, after 18 (left panels) and 24 h of incubation with RBCs (right panels). Each data point is presented as mean ± absolute error (<span class="html-italic">n</span> = 2).</p>
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<p>Comparison between <span class="html-italic">ζ</span>-potential measures (black squares) and EC50 (blue squares) for GO and its functionalized derivatives. <span class="html-italic">ζ</span>-potential data are presented as mean ± standard deviation (<span class="html-italic">n</span> = 3).</p>
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<p>Pro-coagulant activity data for GO. Histograms representing values of t<sub>1/2</sub> for the corresponding concentration of nanomaterial.</p>
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<p>Schematic chemical structure of GO, its derivatives showing different degrees of reduction (top panel), and functionalized derivatives of GO (bottom panel) investigated in this study.</p>
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49 pages, 4695 KiB  
Review
Review of Advances in Coating and Functionalization of Gold Nanoparticles: From Theory to Biomedical Application
by Wilmmer Alexander Arcos Rosero, Angelica Bueno Barbezan, Carla Daruich de Souza and Maria Elisa Chuery Martins Rostelato
Pharmaceutics 2024, 16(2), 255; https://doi.org/10.3390/pharmaceutics16020255 - 9 Feb 2024
Cited by 10 | Viewed by 3807
Abstract
Nanoparticles, especially gold nanoparticles (Au NPs) have gained increasing interest in biomedical applications. Used for disease prevention, diagnosis and therapies, its significant advantages in therapeutic efficacy and safety have been the main target of interest. Its application in immune system prevention, stability in [...] Read more.
Nanoparticles, especially gold nanoparticles (Au NPs) have gained increasing interest in biomedical applications. Used for disease prevention, diagnosis and therapies, its significant advantages in therapeutic efficacy and safety have been the main target of interest. Its application in immune system prevention, stability in physiological environments and cell membranes, low toxicity and optimal bioperformances are critical to the success of engineered nanomaterials. Its unique optical properties are great attractors. Recently, several physical and chemical methods for coating these NPs have been widely used. Biomolecules such as DNA, RNA, peptides, antibodies, proteins, carbohydrates and biopolymers, among others, have been widely used in coatings of Au NPs for various biomedical applications, thus increasing their biocompatibility while maintaining their biological functions. This review mainly presents a general and representative view of the different types of coatings and Au NP functionalization using various biomolecules, strategies and functionalization mechanisms. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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<p>(<b>A</b>) Surface plasmon resonance (SPR) phenomenon involving what happens on the surface of gold nanoparticles when interacting with light. (<b>B</b>) Some types of coatings used for gold nanoparticles, ligands, medicinal agents, DNA, antibody, etc. These interact through covalent-type ligations such as S-Au or electrostatic, and at the same time molecules linked to gold atoms can form interactions such as H-H hydrogen bridges.</p>
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<p>Exploring diverse routes in bottom–up nanoparticle synthesis: from chemical techniques to eco-friendly biological and radiative methods. In the bottom–up approach, there is a wide variety of routes, completely chemical methods such as the Turkevich method and variants, biological methods where microorganisms such as fungi are used, often called eco-friendly, and methods of obtaining the use of gamma radiation.</p>
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<p>Schematic illustration of doxorubicin (DOX)-tethered responsive gold nanoparticles.</p>
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<p>Electrostatic and steric repulsion model. (<b>A</b>) Electrostatic stabilization of AuNPs is based on Coulomb repulsion between particles with the same surface charge sign, preventing the particles from coming into close contact where the attractive short-distance van der Waals forces dominate. (<b>B</b>) For steric stabilization, the contact is avoided by adsorbing bulky molecules on the surface, which act as a spacer to prevent particle aggregation [<a href="#B1-pharmaceutics-16-00255" class="html-bibr">1</a>,<a href="#B44-pharmaceutics-16-00255" class="html-bibr">44</a>].</p>
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<p>Stereochemistry in protecting units on the surface of gold clusters. (<b>A</b>) Schematic drawing of a monomeric Au–SR–Au staple motif. (<b>B</b>) Stereochemistry in protecting units on the surface of gold clusters. While the gold atoms stabilized between two sulfur atoms are formal Au, the gold atoms at the bottom of the structures are Au<sup>0</sup> atoms at the surface of the cluster core (I). The stereodescriptors are indicated in red, and lowercase letters indicate pseudochirality. Priority for the determination of absolute configuration is Au<sup>0</sup> &gt; Au<sup>1</sup> &gt; R &gt; electron lone pair (schematic and image taken from “Chirality in Thiolate-Protected Gold Clusters”) [<a href="#B46-pharmaceutics-16-00255" class="html-bibr">46</a>].</p>
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<p>Au NP protein corona complex. The affinity and exchange rate of the protein crown depend on the size, charge, composition, geometry, incubation conditions (temperature, concentration, time), the type of proteins and their stability. The formation of the crown defines the cellular internalization, biodistribution and toxicity of the particle [<a href="#B47-pharmaceutics-16-00255" class="html-bibr">47</a>,<a href="#B49-pharmaceutics-16-00255" class="html-bibr">49</a>,<a href="#B50-pharmaceutics-16-00255" class="html-bibr">50</a>,<a href="#B51-pharmaceutics-16-00255" class="html-bibr">51</a>].</p>
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<p>Co-functionalization of AuNPs typically employs two techniques. The first method entails producing a mixed monolayer, for instance, by directly adhering PEG and RME to the surface of AuNP using thiol chemistries (<b>A</b>). The second method makes use of a hetero-bifunctional PEG linker, such as thiol-PEGsuccinimidyl glutaramide (SH-PEG-SGA), which has an NHS ester group at one end for attachment to the AuNP surface and a thiol at the other end for direct binding to the RME peptide via the N-terminus group (<b>B</b>). Therefore, the latter configuration has the ability to fully saturate the AuNP surface with PEG before saturating the free end of PEG with a physiologically active group.</p>
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<p>Antibody and protein functionalized Au NPs. (<b>A</b>) Coating of gold nanoparticles with proteins by means of electrostatic interactions. Protein binding association constants on AuNPs increase progressively with AuNP diameter between 5 and 60 nm. The binding association constant, on the other hand, was discovered to be slowly varying for some AuNPs with diameters greater than about 80 nm [<a href="#B99-pharmaceutics-16-00255" class="html-bibr">99</a>]. (<b>B</b>) Functionalization of antibodies by means of a PEG bridge. Every year, more antibodies are used to functionalize Au NPs. Most of these systems are stabilized with thiolated linkers like PEG chains, which are typically terminated in carboxylic acids or succinimidyl esters that are then activated for the addition of antibodies by forming random amide bonds with free amine residues on the surface of the antibodies.</p>
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<p>Peptides and amino acid functionalized Au NPs. (<b>A</b>) Different types of amino acid interactions with bacteria. (<b>B</b>) Nanoparticles allow easy functionalization of peptides for gene delivery, with several types of interactions between the peptide fragments being possible; stability increases [<a href="#B141-pharmaceutics-16-00255" class="html-bibr">141</a>,<a href="#B142-pharmaceutics-16-00255" class="html-bibr">142</a>].</p>
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<p>Methods for conjugating DNA on AuNPs. (<b>A</b>) The typical salt-aging process involving initial DNA adsorption, and gradual increase in NaCl concentration. (<b>B</b>) Attaching DNA in the presence of stabilizing ligands (e.g., surfactants) to improve the colloidal stability of AuNPs. (<b>C</b>) Low-pH loading requiring the DNA containing a poly(A) block to assemble into a parallel duplex. (<b>D</b>) The freezing method does not require additional reagents. (<b>E</b>) Anchoring poly(A) containing nonthiolated DNA on AuNPs with controlled density; a longer poly(A) block yields a lower DNA density (adaptation from Biwu et al.) [<a href="#B164-pharmaceutics-16-00255" class="html-bibr">164</a>].</p>
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<p>Structure and biological activity of carbohydrates that have been functionalized with Au NPs (figure is modified from Xiangyan et al.) [<a href="#B199-pharmaceutics-16-00255" class="html-bibr">199</a>].</p>
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<p>Methods for synthesis of polymeric AuNPs. P-AuNPs have the potential to be used in medicine delivery thanks to advancements in nanotechnology. The “direct synthesis”, “grafting to” and “grafting from” techniques are the main synthetic pathways for P-AuNPs (figure is modified from Muddineti et al.) [<a href="#B288-pharmaceutics-16-00255" class="html-bibr">288</a>].</p>
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<p>Schematic depicting the fabrication of red blood cell (RBC)-membrane-coated Au NPs (adapted from Hu et al.) [<a href="#B305-pharmaceutics-16-00255" class="html-bibr">305</a>].</p>
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<p>Flowchart for Inclusion of Studies Performed.</p>
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21 pages, 10997 KiB  
Article
Mesoporous Silica-Layered Gold Nanorod Core@Silver Shell Nanostructures for Intracellular SERS Imaging and Phototherapy
by Sun-Hwa Seo, Ara Joe, Hyo-Won Han, Panchanathan Manivasagan and Eue-Soon Jang
Pharmaceutics 2024, 16(1), 137; https://doi.org/10.3390/pharmaceutics16010137 - 19 Jan 2024
Cited by 2 | Viewed by 2208
Abstract
Precision diagnosis-guided efficient treatment is crucial to extending the lives of cancer patients. The integration of surface-enhanced Raman scattering (SERS) imaging and phototherapy into a single nanoplatform has been considered a more accurate diagnosis and treatment strategy for cancer nanotheranostics. Herein, we constructed [...] Read more.
Precision diagnosis-guided efficient treatment is crucial to extending the lives of cancer patients. The integration of surface-enhanced Raman scattering (SERS) imaging and phototherapy into a single nanoplatform has been considered a more accurate diagnosis and treatment strategy for cancer nanotheranostics. Herein, we constructed a new type of mesoporous silica-layered gold nanorod core@silver shell nanostructures loaded with methylene blue (GNR@Ag@mSiO2-MB) as a multifunctional nanotheranostic agent for intracellular SERS imaging and phototherapy. The synthesized GNR@Ag@mSiO2-MB nanostructures possessed a uniform core–shell structure, strong near-infrared (NIR) absorbance, photothermal conversion efficiency (65%), dye loading ability, SERS signal, and Raman stability under phototherapy conditions. Under single 785 nm NIR laser irradiation, the intracellular GNR@Ag@mSiO2-MB nanostructures were dramatically decreased to <9%, which showed excellent photothermal and photodynamic effects toward cancer cell killing, indicating that the combination of photothermal therapy (PTT) and photodynamic therapy (PDT) of the GNR@Ag@mSiO2-MB nanostructures could greatly enhance the therapeutic efficacy of cancer cell death. GNR@Ag@mSiO2-MB nanostructures demonstrated a strong Raman signal at 450 and 502 cm−1, corresponding to the δ(C–N–C) mode, suggesting that the Raman bands of GNR@Ag@mSiO2-MB nanostructures were more efficient to detect CT-26 cell SERS imaging with high specificity. Our results indicate that GNR@Ag@mSiO2-MB nanostructures offer an excellent multifunctional nanotheranostic platform for SERS imaging and synergistic anticancer phototherapy in the future. Full article
(This article belongs to the Special Issue Nanodynamic Therapies against Cancer and Microbial Infections)
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<p>TEM images of two different procedures for the synthesis of GNRs (<b>a</b>,<b>b</b>), GNR@Ag (<b>c</b>), GNR@mSiO<sub>2</sub> (<b>e</b>), GNR@Ag@mSiO<sub>2</sub> (<b>d</b>,<b>f</b>), and GNR@Ag@mSiO<sub>2</sub>-MB nanostructures (<b>g</b>).</p>
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<p>(<b>a</b>,<b>b</b>) FETEM images of GNR@Ag@mSiO<sub>2</sub>-MB. Bright-field (<b>c</b>) and dark-field (<b>d</b>) STEM images of GNR@Ag@mSiO<sub>2</sub>-MB. EDX elemental mapping (<b>e</b>) and spectroscopy (<b>f</b>) of GNR@Ag@mSiO<sub>2</sub>-MB.</p>
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<p>(<b>a</b>) UV–vis absorption spectra of GNR, GNR@Ag, GNR@Ag@mSiO<sub>2</sub>, and GNR@Ag@mSiO<sub>2</sub> nanostructure. Size distribution histogram (<b>b</b>) and zeta potential (<b>c</b>) of GNR, GNR@Ag, GNR@Ag@mSiO<sub>2</sub>, and GNR@Ag@mSiO<sub>2</sub> nanostructure.</p>
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<p>Photographic images (<b>a</b>), UV–vis absorption spectra (<b>b</b>), and variation in <span class="html-italic">λ</span><sub>LSPR</sub> for the GNR core (<b>c</b>) and the Ag shell (<b>d</b>) of GNR@Ag@mSiO<sub>2</sub> samples obtained using different volumes of 0.01 M AgCl solution from 25 to 5000 μL.</p>
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<p>TEM images of GNR@Ag@mSiO<sub>2</sub> synthesized using different volumes of 0.01 M AgCl aqueous solutions: (<b>a</b>) 25, (<b>b</b>) 50, (<b>c</b>) 75, (<b>d</b>) 100, (<b>e</b>) 125, (<b>f</b>) 250, (<b>g</b>) 500, (<b>h</b>) 1000, (<b>i</b>) 2500, and (<b>j</b>) 5000 μL. Variation in Ag layer thickness (<b>k</b>) and aspect ratio (<b>l</b>) of GNR@Ag within mSiO<sub>2</sub> layer with the volume of AgCl solution used in the synthesis.</p>
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<p>Anisotropic growth mechanism of the Ag shell on the GNR core.</p>
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<p>Energy-level diagram illustrating plasmon hybridization in GNR@Ag. Blue and red shaded circles represent negative and positive surface charges induced by electromagnetic excitation.</p>
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<p>Micro-Raman spectra (laser wavelength = 785 nm; power = 2 μW; spot area = 51 μm<sup>2</sup>) of MB, GNR@mSiO<sub>2</sub>-MB, and GNR@Ag@mSiO<sub>2</sub> synthesized using different volumes of 0.01 M AgCl solution: (<b>a</b>) 25–5000 μL and (<b>b</b>) 25–500 μL. Change in Raman intensity of δ(C–N–C), ν(C–N), and ν(C–C)<sub>ring</sub> modes at 450, 1398, and 1625 cm<sup>−1</sup> for GNR@Ag@mSiO<sub>2</sub>-MB synthesized different volumes of 0.01 M AgCl solution: (<b>c</b>) 25–5000 μL and (<b>d</b>) 25–500 μL.</p>
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<p>(<b>a</b>) The photothermal heating curves of GNR, GNR@mSiO<sub>2</sub>, GNR@Ag@mSiO<sub>2</sub>, and GNR@Ag@mSiO<sub>2</sub>-MB suspensions under 785 nm laser irradiation (0.6 W/cm<sup>2</sup>) for 600 s. The photothermal heating profiles (<b>b</b>) and IR thermal images (<b>c</b>) of GNR@Ag@mSiO<sub>2</sub>-MB suspension with different volumes (12, 16, 20, and 24 µL of 100 µg/mL) under 785 nm laser irradiation (0.6 W/cm<sup>2</sup>) for 600 s. (<b>d</b>) The photothermal heating curves of GNR@Ag@mSiO<sub>2</sub>-MB under 785 nm (0.6 W/cm<sup>2</sup>) for 600 s, followed by natural cooling down with the laser turning off for 1200 s. (<b>e</b>) Plots of the cooling period versus the negative natural logarithm of driving force temperature. (<b>f</b>) Repeated heating/cooling profiles for five cycles.</p>
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<p>Confocal fluorescence images of CT-26 cells stained with calcein-AM/PI under various treatment groups such as control, control + NIR laser, GNR only, GNR@mSiO<sub>2</sub> only, GNR@Ag@mSiO<sub>2</sub> only, GNR@Ag@mSiO<sub>2</sub>-MB only, and GNR@Ag@mSiO<sub>2</sub>-MB + NIR laser (20× magnification; scale bar: 100 μm).</p>
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<p>Micro-Raman spectra and merged bright-field/Raman mapping images of CT-26 cells treated with MB, GNR@mSiO<sub>2</sub>-MB, and GNR@Ag@mSiO<sub>2</sub>-MB. The color contrast in the mapping images corresponds to the intensity of the δ(C–N–C) vibrational band of MB. The red cross in the bright-field images shows the NIR laser excitation site corresponding to the spectra shown on the left (laser wavelength = 785 nm; power = 2 μW; spot area = 51 μm<sup>2</sup>).</p>
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<p>Schematic illustration of two different procedures for the synthesis of GNR@Ag@mSiO<sub>2</sub> and GNR@Ag@mSiO<sub>2</sub>-MB nanostructures.</p>
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10 pages, 1470 KiB  
Article
MRI Detection and Therapeutic Enhancement of Ferumoxytol Internalization in Glioblastoma Cells
by Michael S. Petronek, Nahom Teferi, Chu-Yu Lee, Vincent A. Magnotta and Bryan G. Allen
Nanomaterials 2024, 14(2), 189; https://doi.org/10.3390/nano14020189 - 13 Jan 2024
Cited by 3 | Viewed by 1804
Abstract
Recently, the FDA-approved iron oxide nanoparticle, ferumoxytol, has been found to enhance the efficacy of pharmacological ascorbate (AscH) in treating glioblastoma, as AscH reduces the Fe3+ sites in the nanoparticle core. Given the iron oxidation state specificity of T2* [...] Read more.
Recently, the FDA-approved iron oxide nanoparticle, ferumoxytol, has been found to enhance the efficacy of pharmacological ascorbate (AscH) in treating glioblastoma, as AscH reduces the Fe3+ sites in the nanoparticle core. Given the iron oxidation state specificity of T2* relaxation mapping, this study aims to investigate the ability of T2* relaxation to monitor the reduction of ferumoxytol by AscH with respect to its in vitro therapeutic enhancement. This study employed an in vitro glioblastoma MRI model system to investigate the chemical interaction of ferumoxytol with T2* mapping. Lipofectamine was utilized to facilitate ferumoxytol internalization and assess intracellular versus extracellular chemistry. In vitro T2* mapping successfully detected an AscH-mediated reduction of ferumoxytol (25.6 ms versus 2.8 ms for FMX alone). The T2* relaxation technique identified the release of Fe2+ from ferumoxytol by AscH in glioblastoma cells. However, the high iron content of ferumoxytol limited T2* ability to differentiate between the external and internal reduction of ferumoxytol by AscH (ΔT2* = +839% for external FMX and +1112% for internal FMX reduction). Notably, the internalization of ferumoxytol significantly enhances its ability to promote AscH toxicity (dose enhancement ratio for extracellular FMX = 1.16 versus 1.54 for intracellular FMX). These data provide valuable insights into the MR-based nanotheranostic application of ferumoxytol and AscH therapy for glioblastoma management. Future developmental efforts, such as FMX surface modifications, may be warranted to enhance this approach further. Full article
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<p><b>Pharmacological perturbations of intracellular iron can be detected in GBM cells using T<sub>2</sub>* mapping.</b> Quantification of in vitro T<sub>2</sub>* maps of human GBM (U87, U251, U118) cells treated with P-AscH<sup>−</sup> (20 pmol cell<sup>-1</sup>; range: 6–8 mM, 1 h) or DFO (200 µM, 24 h). Phosphate-buffered saline without cells was used as a positive control. Values represent the average magnitude of deflection in T<sub>2</sub>* relaxation from control (n = 3).</p>
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<p><b>T<sub>2</sub>* mapping detects FMX internalization and reduction in vitro.</b> (<b>a</b>) Cells were treated for 24 h followed by PBS washing and trypsinization. The large increase in intracellular iron content of FMX-L becomes apparent due to the reddish hue of the cell pellet. (<b>b</b>) Relative [FMX] concentrations in cell culture media following 24 h incubation. This was done by evaluating the EPR spectral peak of FMX at t = 0 and t = 24 h and normalizing both FMX and FMX-L peaks to FMX alone. (<b>c</b>) Intracellular, chelatable iron content in U87 cells following a 24 h incubation with FMX or FMX-L. Error bars represent mean ± SEM with * <span class="html-italic">p</span> &lt; 0.05 using a Welch’s <span class="html-italic">t</span>-test. (<b>d</b>) Representative phase contrast (40×) Prussian blue images for cellular iron content in U87 cells treated with FMX for 1 h and 24 h, or 24 h FMX-L. Black arrows indicate clusters of Prussian blue-positive cells.</p>
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<p><b>FMX internalization enhances AscH<sup>−</sup> cytotoxicity in glioblastoma cells.</b> (<b>a</b>) Representative T<sub>2</sub>* maps of U87 cell pellets treated with 20 pmol cell<sup>−1</sup> AscH<sup>−</sup> ± standard 1 h co-incubation with 20 µg mL<sup>-1</sup> FMX or 24 h pre-treatment with 20 µg mL<sup>−1</sup> FMX-L. (<b>b</b>) Mean T<sub>2</sub>* relaxation times in U87 cells treated with 20 pmol cell<sup>−1</sup> AscH<sup>−</sup> ± standard 1 h co-incubation with 20 µg mL<sup>−1</sup> FMX or 24 h pre-treatment with 20 µg mL<sup>−1</sup> FMX-L. (<b>c</b>) Changes in T<sub>2</sub>* relaxation time (% difference from untreated control) associated with 20 pmol cell<sup>−1</sup> AscH<sup>−</sup> treatment standard 1 h co-incubation with 20 µg mL<sup>−1</sup> FMX or 24 h pre-treatment with 20 µg mL<sup>−1</sup> FMX-L. (<b>d</b>) Clonogenic dose–response curves for U87 cells treated with increasing concentrations of AscH<sup>−</sup> ± standard 1 h co-incubation with 20 µg mL<sup>−1</sup> FMX or 24 h pre-treatment with 20 µg mL<sup>−1</sup> FMX-L. Error bars represent mean ± SEM for three independent experiments with * <span class="html-italic">p</span> &lt; 0.05 using a one-way ANOVA test with a post-hoc Tukey’s test.</p>
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38 pages, 2960 KiB  
Review
Role of Nanoparticle-Conjugates and Nanotheranostics in Abrogating Oxidative Stress and Ameliorating Neuroinflammation
by Tapan A. Patel, Bhavesh D. Kevadiya, Neha Bajwa, Preet Amol Singh, Hong Zheng, Annet Kirabo, Yu-Long Li and Kaushik P. Patel
Antioxidants 2023, 12(10), 1877; https://doi.org/10.3390/antiox12101877 - 18 Oct 2023
Cited by 4 | Viewed by 4033
Abstract
Oxidative stress is a deteriorating condition that arises due to an imbalance between the reactive oxygen species and the antioxidant system or defense of the body. The key reasons for the development of such conditions are malfunctioning of various cell organelles, such as [...] Read more.
Oxidative stress is a deteriorating condition that arises due to an imbalance between the reactive oxygen species and the antioxidant system or defense of the body. The key reasons for the development of such conditions are malfunctioning of various cell organelles, such as mitochondria, endoplasmic reticulum, and Golgi complex, as well as physical and mental disturbances. The nervous system has a relatively high utilization of oxygen, thus making it particularly vulnerable to oxidative stress, which eventually leads to neuronal atrophy and death. This advances the development of neuroinflammation and neurodegeneration-associated disorders such as Alzheimer’s disease, Parkinson’s disease, epilepsy, dementia, and other memory disorders. It is imperative to treat such conditions as early as possible before they worsen and progress to irreversible damage. Oxidative damage can be negated by two mechanisms: improving the cellular defense system or providing exogenous antioxidants. Natural antioxidants can normally handle such oxidative stress, but they have limited efficacy. The valuable features of nanoparticles and/or nanomaterials, in combination with antioxidant features, offer innovative nanotheranostic tools as potential therapeutic modalities. Hence, this review aims to represent novel therapeutic approaches like utilizing nanoparticles with antioxidant properties and nanotheranostics as delivery systems for potential therapeutic applications in various neuroinflammation- and neurodegeneration-associated disease conditions. Full article
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<p>Different nanoparticles (NPs). Schematic representation of various functionalized NPs.</p>
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<p>Mechanisms of action of different functionalized NPs. Schematic representation of internalization of different NPs or specific antioxidants in damaged neurons and their action on various cellular organelles to reduce ROS or scavenge ROS.</p>
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<p>Mechanisms of neuronal damage and its protection by various NPs. Various NPs and their functionalization can protect neuronal cells from neurodegeneration at the structural or functional level by abrogating ROS.</p>
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