[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled.
 
 
Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (2,641)

Search Parameters:
Keywords = nanocarrier

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
22 pages, 3596 KiB  
Article
Chondroitin Sulfate Nanovectorized by LC-PUFAs Nanocarriers Extracted from Salmon (Salmo salar) by Green Process with Decreased Inflammatory Marker Expression in Interleukin-1β-Stimulated Primary Human Chondrocytes In Vitro Culture
by Louis Pruvost, Maureen Gerlei, Cédric Paris, Émilie Velot, Cyril J.-F. Kahn, Arnaud Bianchi and Michel Linder
Mar. Drugs 2024, 22(12), 571; https://doi.org/10.3390/md22120571 - 20 Dec 2024
Abstract
Chondroitin sulfate (CS), a glycosaminoglycan, supports health through various physiological functions, including tissue protection, bone growth, and skin aging prevention. It also contributes to anticoagulant or anti-inflammatory processes, with its primary clinical use being osteoarthritis treatment. This study presents the results of the [...] Read more.
Chondroitin sulfate (CS), a glycosaminoglycan, supports health through various physiological functions, including tissue protection, bone growth, and skin aging prevention. It also contributes to anticoagulant or anti-inflammatory processes, with its primary clinical use being osteoarthritis treatment. This study presents the results of the valorization of lipids and CS, both extracted from salmon co-products through enzymatic processes. The polar lipids, naturally rich in long-chain fatty acids (docosahexaenoic acid DHA C22:6 n-3 and eicosapentaenoic acid EPA C20:5 n-3), and the CS, primarily located in the nasal cartilage, were separated and concentrated before being characterized using various techniques to determine functional and lipid composition. These compounds were then used to formulate liposomes of 63 to 95 nm in size composed of 19.38% of DHA and 7.44% of EPA and encapsulating CS extract with a Δdi-4S/Δdi-6S ratio of 0.53 at 2 weight masses (10–30 kDa and >30 kDa) or CS standard all at two different concentrations. Liposomes were tested on human chondrocytes in inflamed conditions. Thus, compatibility tests, the expression of various inflammation markers at transcriptional and molecular levels, nitrites, and the amount of collagenase produced were analyzed. The results showed that CS, in synergy with the liposomes, played a positive role in combating chondrocyte inflammation even at a low concentration. Full article
(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)
Show Figures

Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>FT-IR spectra of (<b>a</b>) CS and (<b>b</b>) lipids all extracted from <span class="html-italic">Salmo salar</span> heads by enzymatic hydrolysis.</p>
Full article ">Figure 2
<p>Monitoring Δdi-4S and Δdi-6S disaccharides in (<b>a</b>) reference mixture of hydrolyzed commercial marine CS by UV<sub>240</sub> in panel 1 and by MS<sup>2</sup> in panels 2 (specific screening of delta Δdi-4S with daughter ion <span class="html-italic">m</span>/<span class="html-italic">z</span> = 300) and 3 (specific screening of delta Δdi-6S with daughter ion <span class="html-italic">m</span>/<span class="html-italic">z</span> = 282); and in (<b>b</b>) sample of interest by UV<sub>240</sub> for semi-quantitative evaluation.</p>
Full article ">Figure 3
<p>Biocompatibility of liposomes with CS with human chondrocytes. Human chondrocytes exposed to nanoliposomes (250 μg/mL) or nanoliposomes and CS extracts (250 μg/mL + 125 or 25 μg/mL) for 1 days. (<b>A</b>) Lactate Deshydrogenase (LDH) release determined as described under <a href="#sec3-marinedrugs-22-00571" class="html-sec">Section 3</a>. Metabolic activity assessed using MTT assay. (<b>B</b>) Cell metabolic activity results on different membranes presented in % vs. control results (as 100%). (<b>C</b>) DNA concentrations measured to estimate proliferation of cells. Results shown are mean ± SD of at least four individual experiments. *: <span class="html-italic">p</span> &lt; 0.01, compared to control.</p>
Full article ">Figure 4
<p>Effect of nanoliposomes/CS exposure on IL-1β-stimulated Cox/mPGES pathways. Human chondrocytes stimulated or not with 1 ng/mL IL-1β and exposed to nanoliposomes (250 µg/mL) or nanoliposomes and CS extracts (250 µg/mL + 25 µg/mL). For (<b>A</b>,<b>B</b>,<b>D</b>,<b>F</b>), culture conditions performed for 6 h for early inflammation markers (COX-2 and iNOS mRNA) and 24 h (Aggrecan and mPGES-1 mRNA). Total RNA extracted, then reverse transcribed into cDNA and analyzed by Real-Time Polymerase Chain Reaction (RT-PCR). Relative abundance of Cox-2, mPGES, iNOS, and Aggrecan mRNAs normalized to Retinitis Pigmentosa 29 (RP29) mRNA. Comparison made by using ΔCt method with fold value of reference = 1. Results shown are mean ± SD of at least four individual experiments (*: <span class="html-italic">p</span> &lt; 0.01 vs. control; #: <span class="html-italic">p</span> &lt; 0.01 versus IL-1β). For (<b>C</b>,<b>E</b>), culture conditions performed for 48 h for PGE2 and of nitrites (*: <span class="html-italic">p</span> &lt; 0.01 vs. control; #: <span class="html-italic">p</span> &lt; 0.01 vs. IL-1β).</p>
Full article ">Figure 5
<p>The effect of nanoliposomes/CS exposure on IL-1β-stimulated MMPs. Human chondrocytes were stimulated or not with 1 ng/mL IL-1β and exposed to nanoliposomes (250 µg/mL) or nanoliposomes and CS extracts (250 µg/mL+ 25 µg/mL). For (<b>A</b>,<b>B</b>,<b>E</b>), total RNA was extracted after 24 h stimulation then reverse transcribed into cDNA and analyzed by RT-PCR. The relative abundance of MMP1, MMP3, and MMP13 mRNAs was normalized to RP29 mRNA. Comparison was performed using the ΔCt method with the fold value of reference = 1. The results shown are the mean ± SD of at least four individual experiments (*: <span class="html-italic">p</span> &lt; 0.01 vs. control; #: <span class="html-italic">p</span> &lt; 0.01 vs. IL-1β). For (<b>C</b>,<b>D</b>,<b>F</b>) levels of MMP1, 3, and 13 after 48 h of stimulation (*: <span class="html-italic">p</span> &lt; 0.01 vs. control; #: <span class="html-italic">p</span> &lt; 0.01 vs. IL-1β).</p>
Full article ">Figure 6
<p>Recapitulative graphical abstract of study design and objectives.</p>
Full article ">Figure A1
<p>Calibration range of 4S and 6S isomers.</p>
Full article ">
18 pages, 1238 KiB  
Review
Nanocarriers Responsive to Light—A Review
by Ismat F. Almadani, Mohammad F. Almadani, Nour AlSawaftah, Waad H. Abuwatfa and Ghaleb A. Husseini
Micro 2024, 4(4), 827-844; https://doi.org/10.3390/micro4040051 - 20 Dec 2024
Abstract
The non-specific and minimally selective nature of traditional drug administration methods, along with various other limitations, makes the use of drug delivery systems more favorable. Light-responsive, or light-triggered, drug delivery systems provide more controlled and less invasive treatment approaches, addressing the shortcomings of [...] Read more.
The non-specific and minimally selective nature of traditional drug administration methods, along with various other limitations, makes the use of drug delivery systems more favorable. Light-responsive, or light-triggered, drug delivery systems provide more controlled and less invasive treatment approaches, addressing the shortcomings of traditional methods. In this paper, we reviewed studies utilizing light-triggered nanoparticles (NPs) for treating cancer and various other diseases, focusing on photodynamic therapy (PDT) and photothermal therapy (PTT) in both in vivo and in vitro applications. Most of the reviewed studies employed synergistic approaches that combined PDT or PTT with other therapeutic methods to leverage the strengths of both techniques and enhance treatment efficiency or to overcome the individual limitations of each method, which is discussed extensively in this paper. Full article
Show Figures

Figure 1

Figure 1
<p>The structure of Nanospheres VS Nanocapsules.</p>
Full article ">Figure 2
<p>Mechanism of PDT.</p>
Full article ">Figure 3
<p>Mechanism of PTT.</p>
Full article ">
14 pages, 4878 KiB  
Article
Efficient mRNA Delivery In Vitro and In Vivo Using a Polycharged Biodegradable Nanomaterial
by Xuejin Yang, Jingya Xiao, Daryl Staveness and Xiaoyu Zang
Int. J. Mol. Sci. 2024, 25(24), 13620; https://doi.org/10.3390/ijms252413620 - 19 Dec 2024
Abstract
As RNA rises as one of the most significant modalities for clinical applications and life science research, efficient tools for delivering and integrating RNA molecules into biological systems become essential. Herein, we report a formulation using a polycharged biodegradable nano-carrier, N1-501, which demonstrates [...] Read more.
As RNA rises as one of the most significant modalities for clinical applications and life science research, efficient tools for delivering and integrating RNA molecules into biological systems become essential. Herein, we report a formulation using a polycharged biodegradable nano-carrier, N1-501, which demonstrates superior efficiency and versatility in mRNA encapsulation and delivery in both cell and animal models. N1-501 is a polymeric material designed to function through a facile one-step formulation process suitable for various research settings. Its capability for mRNA transfection is investigated across a wide range of mRNA doses and in different biological models, including 18 tested cell lines and mouse models. This study also comprehensively analyzes N1-501’s application for mRNA transfection by examining factors such as buffer composition and pH, incubation condition, and media type. Additionally, N1-501’s superior in vivo mRNA transfection capability ensures its potential as an efficient and consistent tool for advancing mRNA-based therapies and genetic research. Full article
(This article belongs to the Special Issue Polymers in Biological Systems)
Show Figures

Figure 1

Figure 1
<p>N1-501 effectively delivers mRNA across various cell lines as compared with Lipofectamine 3000. (<b>A</b>) The transfection efficiency was evaluated after 24 h of treatment. (<b>B</b>) Fluorescence microscopy images of 18 cell lines were captured 24 h after transfection to visualize eGFP expression levels. (Scale bar, 400 µm).</p>
Full article ">Figure 2
<p>N1-501 demonstrated high spleen tropism during in vivo transfection. (<b>A</b>) In vivo bioluminescence (3, 6, and 12 h) and ex vivo bioluminescence (6 h) of major organs excised from Balb/c mice i.v. injected with N1-501/Fluc mRNA. (<b>B</b>) Quantification of total bioluminescence in various organs. (<b>C</b>) Quantification of total bioluminescence in mice at different time points.</p>
Full article ">Figure 3
<p>Graphical depiction of operationally simple transfection protocols developed for N1-501.</p>
Full article ">Figure 4
<p>The transfection performance and safety profiles of N1-501 at varied mRNA and reagent dose combinations. Black dots represent specific formulation conditions used in the study; the contour plot is filled with simulated data. (<b>A</b>) The contour plot for GFP expression, represented by MFI, was measured using a high-content screening system 24 h after transfection. (<b>B</b>) The contour plot showing the percentage of GFP-positive cells 24 h after transfection. (<b>C</b>) The contour plot showing HEK 293T cell viability 24 h after treatment with N1-501/eGFP mRNA complexes. Viability was evaluated using the CCK-8 assay.</p>
Full article ">Figure 5
<p>Buffer and medium compatibility during formulation and transfection. N1-501 was diluted in 10 mM citrate buffer (pH = 4.0, 5.0, 6.0), 10 mM acetate buffer (pH = 4.0, 5.0, 6.0), 1X PBS buffer (pH = 7.4), 10 mM HEPES buffer (pH = 8.0), and water, respectively. After mixing with mRNA, the nanoparticle was diluted in Opti-MEM reduced-serum medium, serum-free DMEM [DMEM(−/−)], DMEM with 10% FBS [DMEM(10% FBS)], or DMEM containing 10% FBS and 1% penicillin/streptomycin [DMEM(+/+)] and applied to cells in the same media. The MFI (<b>A</b>) and percentage of GFP-positive cells (<b>B</b>) were assessed 24 h after transfection. Data are shown as the mean ± SD. Statistical significance was determined using an unpaired two-tailed Student’s <span class="html-italic">t</span> test (ns: no significance, **** <span class="html-italic">p</span> &lt; 0.0001).</p>
Full article ">Figure 6
<p>Effect of pre-incubation time on mRNA delivery by N1-501. N1-501 was formulated with eGFP mRNA and then held at 0 °C, 25 °C, and 37 °C for different lengths of time. (<b>A</b>) MFI and (<b>B</b>) percentage of GFP-positive cells were measured 24 h after transfection. Data are shown as the mean ± SD. Statistical significance was determined using an unpaired two-tailed Student’s <span class="html-italic">t</span> test (ns: no significance, ** <span class="html-italic">p</span> &lt; 0.01).</p>
Full article ">Figure 7
<p>N1-501’s shelf life, evaluated by transfection efficacy in vitro. (<b>A</b>) MFI and (<b>B</b>) percentage of GFP-positive cells were assessed 24 h after transfection. Data are shown as the mean ± SD. Statistical significance was determined using an unpaired two-tailed Student’s <span class="html-italic">t</span> test (ns: no significance, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001).</p>
Full article ">
21 pages, 4369 KiB  
Article
Development of Liver-Targeting αVβ5+ Exosomes as Anti-TGF-β Nanocarriers for the Treatment of the Pre-Metastatic Niche
by Paloma Acosta Montaño, Eréndira Olvera Félix, Veronica Castro Flores, Arturo Hernández García, Ruben D. Cadena-Nava, Octavio Galindo Hernández, Patricia Juárez and Pierrick G. J. Fournier
Biology 2024, 13(12), 1066; https://doi.org/10.3390/biology13121066 - 19 Dec 2024
Abstract
Liver metastases frequently occur in pancreatic and colorectal cancer. Their development is promoted by tumor-derived exosomes with the integrin αVβ5 on their membrane. This integrin directs exosomes to the liver, where they promote a TGF-β-dependent pre-metastatic niche. We proposed the [...] Read more.
Liver metastases frequently occur in pancreatic and colorectal cancer. Their development is promoted by tumor-derived exosomes with the integrin αVβ5 on their membrane. This integrin directs exosomes to the liver, where they promote a TGF-β-dependent pre-metastatic niche. We proposed the development of αVβ5+ exosomes to deliver anti-TGF-β therapy to the liver. This study demonstrates that the overexpression of αVβ5 in 293T cells allows its transfer to the secreted exosomes. αVβ5 overexpression increases exosome delivery to the liver, and αVβ5+ exosomes accumulate more in the liver compared to the lungs, kidneys, and brain in mice. We then sought 293T cells to directly produce and load an anti-TGF-β agent in their exosomes. First, we transduced 293T cells to express shRNAs against Tgfb1; however, the exosomes isolated from these cells did not knock down Tgfb1 in treated macrophages in vitro. However, when 293T expressed an mRNA coding a soluble form of betaglycan (sBG), a TGF-β inhibitor, this mRNA was detected in the isolated exosomes and the protein in the conditioned media of macrophages treated in vitro. In turn, this conditioned media decreased the TGF-β-induced phosphorylation of SMAD2/3 in hepatic cells in vitro. Our findings suggest that αVβ5+ exosomes could serve as nanocarriers for liver-targeted anti-TGF-β therapies. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Cancer Metastasis)
Show Figures

Figure 1

Figure 1
<p>Integrin expression in 293T cells and validation of isolated exosomes. (<b>A</b>) Expression of the integrins α<sub>v</sub> (<b>left</b>), β<sub>5</sub> (<b>middle</b>), and α<sub>v</sub>β<sub>5</sub> (<b>right</b>) in 293T cells using flow cytometry. Results are presented as histograms. (<b>B</b>) Western blot analysis of the exosomal marker CD81 in whole cell lysates (WCL) and exosomes (Exo) from 293T cells. (<b>C</b>) Measurement of the hydrodynamic diameter of the exosomes isolated from 293T cells. Results are presented as a histogram of the particle size distribution. (<b>D</b>) Characterization of the exosome morphology and size using TEM. Results are presented as a representative image (<b>left</b>; arrows indicate the exosomes) and a histogram (<b>right</b>) of the exosome size distribution.</p>
Full article ">Figure 2
<p>Exosomes from 293T cells localized to the liver. (<b>A</b>) Fluorescence microscopy of RAW 264.7 cells cultured for 24 h with a control solution (PBS<sup>SP-DiIC</sup>) or 293T cell-derived exosomes (3 μg/cm<sup>2</sup>) stained with SP-DiIC<sub>18</sub> (Exosome<sup>SP-DiIC</sup>) (2.5 µM SP-DiIC<sub>18</sub>). (<b>B</b>) Confocal microscopy of liver sections from mice inoculated with a control solution (PBS<sup>SP-DiIC</sup>) or SP-DiIC<sub>18</sub>-stained exosomes from 293T cells (Exosome<sup>SP-DiIC</sup>) (5.0 µM SP-DiIC<sub>18</sub>). Results are presented as representative images of liver sections (<b>left</b>, arrows indicate exosome foci) and the quantification (<b>right</b>) of exosome-positive (Exo<sup>+</sup>) areas by fluorescence imaging in arbitrary units (a.u.) (<span class="html-italic">N</span> = 2 per group) and compared using an unpaired Student’s <span class="html-italic">t</span>-test.</p>
Full article ">Figure 3
<p>Modification and selection of 293T cells overexpressing the integrin α<sub>v</sub>β<sub>5</sub>. (<b>A</b>) Western blot analysis of the expression of the exogenous integrin subunits ITGAV-HA and ITGB5-T7 in untransfected 293T cells (Prtl), after transfection and antibiotic selection (Pool), or after selection of 2 clones, clone 1 (C1) and clone 2 (C2). α-tubulin was used as a loading control. (<b>B</b>) Flow cytometry analysis of the basal fluorescence of 293T cells (Isotype), the expression of α<sub>v</sub>β<sub>5</sub> in untransfected cells (Parental), after transfection and antibiotic selection (Pool), and after selection of clones using limited dilution (clone 1 and clone 2). Results are presented as histograms, with the number indicating the percentage of cells overexpressing α<sub>v</sub>β<sub>5</sub>. (<b>C</b>) Flow cytometry analysis of α<sub>v</sub>β<sub>5</sub> expression in clone 1 and clone 2 after being cultured for 2 weeks with and without hygromycin as a transfection stability assay. Flow cytometry results are represented as histograms. (<b>D</b>) Flow cytometry analysis of the expression of the integrins α<sub>v</sub>, β<sub>5,</sub> and the α<sub>v</sub>β<sub>5</sub> dimer in parental cells and clone 2. Results are presented as histograms (<b>left</b>) with the number indicating the percentage of clone 2 cells overexpressing α<sub>v</sub>β<sub>5</sub> and a bar graph (<b>right</b>) showing the fold-change of integrin expression and the average ± SEM of the mean fluorescence intensity (MFI) of stained cells. Results were compared using a 1-way ANOVA with Tukey’s post hoc test. a.u., arbitrary unit.</p>
Full article ">Figure 4
<p>α<sub>v</sub>β<sub>5</sub><sup>+</sup> exosomes derived from 293T-α<sub>v</sub>β<sub>5</sub><sup>+</sup> cells carry the exogenous integrin and are internalized in RAW 264.7 macrophages in vitro. (<b>A</b>) Western blot analysis of the levels of the exogenous integrin subunit ITGB5-T7 in exosomes isolated from parental 293T cells (Exo-Prtl) and from 293T-α<sub>v</sub>β<sub>5</sub><sup>+</sup> cells (Exo-α<sub>v</sub>β<sub>5</sub>). CD81 was used as a loading control. (<b>B</b>) Measurement of the hydrodynamic diameter of the exosomes isolated from 293T cells, either parental (Exo-Prtl) or α<sub>v</sub>β<sub>5</sub><sup>+</sup> (Exo-α<sub>v</sub>β<sub>5</sub>). Results are presented as a histogram of the particle size distribution. (<b>C</b>) Fluorescence microscopy of RAW 264.7 cells incubated for 24 h with a control solution (PBS<sup>SP-DiIC</sup>) or SP-DiIC<sub>18</sub>-stained exosomes (3.0 µg/cm<sup>2</sup>, red) isolated from parental 293T cells (Exo-Prtl<sup>SP-DiIC</sup>) and from 293T-α<sub>v</sub>β<sub>5</sub><sup>+</sup> cells (Exo-α<sub>v</sub>β<sub>5</sub><sup>SP-DiIC</sup>) (1.0 µM SP-DiIC<sub>18</sub>). Nuclei were stained with DAPI (blue). (<b>D</b>) RAW 264.7 cells were cultured for 24 h in the presence or absence of Exo-Prtl or Exo-α<sub>v</sub>β<sub>5</sub> exosomes (1.5–6.0 µg/cm<sup>2</sup>) stained with SP-DiIC<sub>18</sub> (1.0 µM) before analyzing cells by flow cytometry. Results are presented as the percentage of exosome-positive RAW 264.7 cells (upper bar graph) and the average ± SEM of the mean fluorescence intensity (MFI, a.u., bottom bar graph). (<b>E</b>) Western blot analysis of T7 tag (ITGB5) levels in cell lysates of RAW 264.7 cells incubated for 24 h with PBS, Exo-Prtl exosomes, or Exo-α<sub>v</sub>β<sub>5</sub> exosomes (3.0 µg/cm<sup>2</sup>). α-tubulin was used as a loading control.</p>
Full article ">Figure 5
<p>The overexpression of the integrin α<sub>v</sub>β<sub>5</sub> increases exosome accumulation in the liver. Mice were inoculated with 40 µg of exosomes from parental 293T cells (Exo-Prtl<sup>SP-DiIC</sup>) or 293T-α<sub>v</sub>β<sub>5</sub><sup>+</sup> cells (Exo-α<sub>v</sub>β<sub>5</sub><sup>SP-DiIC</sup>) stained with SP-DiIC<sub>18</sub> (red) or with a control solution (PBS<sup>SP-DiIC</sup>) (5.0 µM SP-DiIC<sub>18</sub>). The next day, the liver, lungs, kidneys, and brain were collected, and cryosections with DAPI counterstaining (blue) were analyzed using a confocal microscope. Results are presented as (<b>left</b>) representative images of tissue sections and (<b>right</b>) the quantification of exosome-positive (Exo<sup>+</sup>) areas by fluorescence imaging in arbitrary units (a.u.) and were compared using a 2-way ANOVA with Tukey’s post hoc test. Scale bars indicate 50 µm. See also <a href="#app1-biology-13-01066" class="html-app">Supplemental Figure S1</a>.</p>
Full article ">Figure 6
<p>Exosomes from 293T cells expressing shTgfb1 do not knock down <span class="html-italic">Tgfb1</span> in RAW cells. 4T1 and 293T-α<sub>V</sub>β<sub>5</sub> cells were transduced with pLKO.1-shGFP, pLKO.1-shTgfb1<sup>1</sup>, pLKO.1-shTgfb1<sup>2</sup>, or both shTgfb1 plasmids (shTgfb1<sup>1&amp;2</sup>) and selected with puromycin. (<b>A</b>) After antibiotic selection, <span class="html-italic">Tgfb1</span> expression was evaluated by qRT-PCR in parental and transduced 4T1 cells with pLKO.1-shGFP, pLKO.1-shTgfb1<sup>1</sup>, pLKO.1-shTgfb1<sup>2</sup>, or both shTgfb1 plasmids (shTgfb1<sup>1&amp;2</sup>), and results were compared using a 1-way ANOVA with Tukey’s post hoc test. (<b>B</b>) Exosomes derived from 293T-α<sub>V</sub>β<sub>5</sub> (Control), 293T-α<sub>V</sub>β<sub>5</sub>-shGFP, 293T-α<sub>V</sub>β<sub>5</sub>-shTgfb1<sup>1</sup>, 293T-α<sub>V</sub>β<sub>5</sub>-shTgfb1<sup>2</sup>, or 293T-α<sub>V</sub>β<sub>5</sub>-shTgfb1<sup>1&amp;2</sup> were isolated and added to RAW 264.7 cultures for 8, 12, or 24 h, and <span class="html-italic">Tgfb1</span> expression was evaluated by qRT-PCR. Results were compared using a 1-way ANOVA with Tukey’s post hoc test. See also <a href="#app1-biology-13-01066" class="html-app">Supplemental Figure S2</a>.</p>
Full article ">Figure 7
<p>Exosome-mediated expression of soluble betaglycan decreases SMAD2/3 phosphorylation. 293T cells were transduced with pLJM1-sBG-Myc wild-type plasmid or pLJM1-sBG-Myc plasmid modified with exosome zipcode sequences in the 3′ UTR: Zip<sup>1</sup>, Zip<sup>2</sup>, and Zip<sup>1&amp;2</sup>. (<b>A</b>) Evaluation of sBG mRNA expression by qRT-PCR in whole cell lysates (WCL) and exosomes from untransduced 293T cells (Prtl) or 293T cells transduced to express sBG-Myc, either wild type (WT) or with exosome zipcode sequences in the 3′ UTR: Zip<sup>1</sup>, Zip<sup>2</sup>, and Zip<sup>1&amp;2</sup>. The results were compared using a 1-way ANOVA with Tukey’s post hoc test. (<b>B</b>) Western blot analysis of sBG-Myc in 293T (Prtl), 293T-sBG (Wt), 293T-sBG-Zip<sup>1</sup>, 293T-sBG-Zip<sup>2</sup>, and 293T-sBG-Zip<sup>1&amp;2</sup> cells in conditioned media. Numbers above membranes show quantitative analysis of Myc tag (sBG) expression. (<b>C</b>) RAW 264.7 cells were incubated for 24 h with 2 μg/cm<sup>2</sup> of 293T-sBG-Zip<sup>1</sup> cell-derived exosomes, and sBG mRNA expression was evaluated in treated cells using qRT-PCR and compared using an unpaired Student’s <span class="html-italic">t</span>-test. (<b>D</b>) Western blot analysis of the conditioned media of RAW 264.7 cells treated or not treated with 1 or 2 μg/cm<sup>2</sup> of 293T-sBG-Zip<sup>1</sup>-cell-derived exosomes to detect the presence of sBG-Myc. The conditioned media of 293T-sBG-Zip<sup>1</sup> cells were used as a positive control. (<b>E</b>) HepG2 cells were incubated for 24 h with complete EMEM media or the conditioned media of RAW 264.7 cells (Ctrl) or RAW cells treated with 2 μg/cm<sup>2</sup> of exosomes derived from 293T-sBG-Zip<sup>1</sup> cells. Results are presented as a Western blot (<b>left</b>) of phosphorylated and total SMAD2/3 (P-SMAD2/3 and SMAD2/3, respectively) and quantification (<b>right</b>) of the phospho/total SMAD2/3 ratio. α-tubulin was used as a loading control. See also <a href="#app1-biology-13-01066" class="html-app">Supplemental Figure S3</a>.</p>
Full article ">
26 pages, 3623 KiB  
Review
Metal Oxide Nanoparticles as Efficient Nanocarriers for Targeted Cancer Therapy: Addressing Chemotherapy-Induced Disabilities
by Mohamed Taha Yassin, Fatimah O. Al-Otibi, Sarah A. Al-Sahli, Mohammad S. El-Wetidy and Sara Mohamed
Cancers 2024, 16(24), 4234; https://doi.org/10.3390/cancers16244234 - 19 Dec 2024
Abstract
Cancer remains a predominant global health concern, necessitating effective treatment options. Conventional cancer therapies, particularly chemotherapy, often face constraints such as low selectivity, insufficient solubility, and multidrug resistance (MDR), which diminish effectiveness and exacerbate negative effects. Metal oxide nanoparticles (MONPs), such as iron [...] Read more.
Cancer remains a predominant global health concern, necessitating effective treatment options. Conventional cancer therapies, particularly chemotherapy, often face constraints such as low selectivity, insufficient solubility, and multidrug resistance (MDR), which diminish effectiveness and exacerbate negative effects. Metal oxide nanoparticles (MONPs), such as iron oxide, zinc oxide, and copper oxide, offer a promising solution by enhancing targeted drug delivery, reducing systemic toxicity, and mitigating chemotherapy-induced disabilities like neurotoxicity and cardiotoxicity. Nanocarriers conjugated with drugs can improve drug delivery within the body and enhance their circulation in the bloodstream. Recent advancements in MONP synthesis and functionalization have further improved their stability and drug-loading capacity, making them a valuable tool in cancer treatment. MONPs have distinctive physicochemical characteristics, enabling better imaging, drug encapsulation, and targeted medication delivery to cancerous cells. These nanocarriers enhance treatment effectiveness through focused and controlled drug release, reducing off-target effects and addressing drug resistance. This review aims to explore the potential of MONPs as efficient nanocarriers for anticancer drugs, addressing limitations of traditional chemotherapy such as poor specificity, systemic toxicity, and drug resistance. Additionally, the review discusses recent advancements in MONP synthesis and functionalization, which enhance their stability, drug-loading capacity, and compatibility. Full article
(This article belongs to the Collection Cancer Nanomedicine)
Show Figures

Figure 1

Figure 1
<p>Different types of nanocarriers are used for the targeted therapy of cancer.</p>
Full article ">Figure 2
<p>Diagrammatic illustration of the critical steps in using metal oxide nanoparticles for targeted cancer treatment. Each step delineates a phase in the process, including synthesis, surface functionalization, drug loading, targeted delivery, cellular uptake, and finally, the therapeutic impact.</p>
Full article ">Figure 3
<p>Synthesis of the metal oxide nanoparticles through bottom-up and top-down approaches.</p>
Full article ">Figure 4
<p>Active targeted therapy of cancer using chemotherapeutic drugs loaded on nanocarriers.</p>
Full article ">Figure 5
<p>Magnetic nanoparticles and chemotherapy agents are administered together in a polymer coating. Upon reaching the cancer site, magnetic nanoparticles are heated by an external magnetic field, removing the polymer coating and releasing chemotherapeutic drugs to the tumor site.</p>
Full article ">Figure 6
<p>(<b>A</b>) DOX was loaded into folate-conjugated dual-responsive magnetic nanoparticles as described. (<b>B</b>) Female Sprague Dawley rats were subcutaneously injected with DMBA at 45–48 days to induce breast tumor. (<b>C</b>) The experiment began after the tumor volume reached 1000 mm<sup>3</sup>. The breast cancer model was given DOX-FA-poly-MNPs at a dosage of 2 mg/kg/48 h. (<b>D</b>) Folate-targeted nanoparticles aggregate at tumor locations via the increased EPR effect, also known as passive targeting. Tumor-targeted nanoparticles attach to cell surface folate receptor-α (FOLR1) via FRs-mediated endocytosis, boosting their entrance into tumor cells, a process known as active targeting. Copyright @ 2022 Pourradi et al. [<a href="#B92-cancers-16-04234" class="html-bibr">92</a>].</p>
Full article ">Figure 7
<p>Illustration of potential MTX-ZnONP internalization through caveolin-mediated endocytosis and the mechanism of MTX action in A549 cells. Copyright @ 2023 Mishra et al. [<a href="#B122-cancers-16-04234" class="html-bibr">122</a>].</p>
Full article ">Figure 8
<p>(<b>a</b>) Diagram depicting the synthesis process of the CuO-NiO@PDA-PTX/FA drug delivery system. (<b>b</b>) Conceptual illustration of the CuO-NiO@PDA-PTX/FA noncomplex, highlighting the combination of bimetallic oxide nanoparticles and a chemotherapeutic agent for enhanced breast cancer treatment. Copyright @ 2023 Singh and Pal 2023 [<a href="#B142-cancers-16-04234" class="html-bibr">142</a>].</p>
Full article ">
17 pages, 2205 KiB  
Article
Exploring Metal Cluster Interactions with Functionalized Graphene via Molecular Dynamics Simulation
by Miriam Roldán-Matilla, Arisbel Cerpa-Naranjo and Isabel Lado-Touriño
C 2024, 10(4), 107; https://doi.org/10.3390/c10040107 - 18 Dec 2024
Viewed by 230
Abstract
Abstract: This study investigates the interaction between copper (Cu) and silver (Ag) clusters and graphene-based materials using molecular dynamics simulations. It focuses on how graphene oxidation and aminated polyethylene glycol (PEG-NH2) functionalization influence interaction strength and cluster dynamics. The analysis includes [...] Read more.
Abstract: This study investigates the interaction between copper (Cu) and silver (Ag) clusters and graphene-based materials using molecular dynamics simulations. It focuses on how graphene oxidation and aminated polyethylene glycol (PEG-NH2) functionalization influence interaction strength and cluster dynamics. The analysis includes pristine graphene (PG), low-oxidized graphene oxide (GOL), and PEGylated graphene oxide (GO-PEG-NH2). The results reveal that clusters on PG exhibit high mobility, while GO-PEG-NH2 significantly restricts mobility due to strong interactions, as evidenced by highly negative interaction energies. GO-PEG-NH2 systems also display pronounced subdiffusive behavior (α < 1), indicating strong binding and constrained motion. These findings underscore the critical role of PEG-NH2 functionalization in controlling cluster diffusion, paving the way for innovative designs in biomedical and catalytic nanocarrier applications. Full article
(This article belongs to the Special Issue Carbon Nanohybrids for Biomedical Applications (2nd Edition))
Show Figures

Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Molecular models used to study interactions between Cu and Ag clusters and graphene-based materials. Atom colors: carbon (C) in gray, hydrogen (H) in white, copper (Cu) in brown, silver (Ag) in light blue, oxygen (O) in red, and nitrogen (N) in blue. Graphene sheet dimensions: 36 × 36 Å<sup>2</sup>; Cu cluster diameter: 4.18 Å; Ag cluster diameter: 4.94 Å (maximum vertex-to-vertex distance).</p>
Full article ">Figure 2
<p>Models used to investigate interactions between metallic clusters and graphene-based materials. Atom color scheme: carbon (C) in gray, hydrogen (H) in white, copper (Cu) in brown, silver (Ag) in light blue, oxygen (O) in red, and nitrogen (N) in blue. The water molecules are represented as red lines.</p>
Full article ">Figure 3
<p>Interaction energies for the adsorption of Cu and Ag clusters on PG and functionalized graphene-based materials.</p>
Full article ">Figure 4
<p>Final positions of Cu and Ag clusters on pristine and functionalized graphene surfaces after 1000 ps of simulation time. Color codes: C—gray, H—white, Cu—brown, Ag—light blue, O—red, N—blue.</p>
Full article ">Figure 5
<p>RDF between the center of mass of the cluster and the surface of graphene-derived materials.</p>
Full article ">Figure 6
<p>Positions of the first two peaks of the RDF between the clusters and graphene-derived material.</p>
Full article ">Figure 7
<p>The time-dependent variation in the distance between the cluster center of mass and the surface of the graphene-derived material.</p>
Full article ">Figure 8
<p>MSD of the cluster center of mass versus the simulation length.</p>
Full article ">
15 pages, 4876 KiB  
Article
Exploring Micelles and Nanospheres as Delivery Systems for Phenothiazine Derivatives in Cancer Therapy
by Katarzyna Jelonek, Monika Musiał-Kulik, Małgorzata Pastusiak, Aleksander Foryś, Andrzej Zięba and Janusz Kasperczyk
Pharmaceutics 2024, 16(12), 1597; https://doi.org/10.3390/pharmaceutics16121597 - 16 Dec 2024
Viewed by 402
Abstract
Objectives: Cancer remains one of the leading causes of death worldwide, and thus, there is a need for the development of innovative and more effective treatment strategies. The aim of the study was to evaluate two types of nanoparticles—nanospheres and micelles—obtained from [...] Read more.
Objectives: Cancer remains one of the leading causes of death worldwide, and thus, there is a need for the development of innovative and more effective treatment strategies. The aim of the study was to evaluate two types of nanoparticles—nanospheres and micelles—obtained from PLA-based polymers to discover their potential for delivering four types of phenothiazine derivatives. Methods: The morphology, drug-loading properties, cytocompatibility, hemolytic properties and anticancer activity were analyzed. Results: The micelles exhibited significantly higher drug-loading properties, release process and cytotoxic activity against cancer cells compared to the nanospheres. The micelles containing 5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride with an OH group as a substituent in the 10-position of the quinobenzothiazine ring showed the highest drug-loading content, the most efficient drug release, the lowest hemolytic activity and the most significant cytotoxic effect against HeLa cells. Conclusions: The conducted study enabled the development of a delivery system for the new anticancer compound and showed that the choice of drug carrier has a crucial effect on its cytotoxic potential against cancer cells. Full article
Show Figures

Figure 1

Figure 1
<p>SEM images of nanospheres loaded with <b>3a</b> (<b>A</b>), <b>3b</b> (<b>B</b>), <b>3c</b> (<b>C</b>) and <b>3d</b> (<b>D</b>).</p>
Full article ">Figure 2
<p>TEM images of micelles loaded with <b>3a</b> (<b>A</b>), <b>3b</b> (<b>B</b>), <b>3c</b> (<b>C</b>) and <b>3d</b> (<b>D</b>).</p>
Full article ">Figure 3
<p>Comparison of drug release from various micellar formulations.</p>
Full article ">Figure 4
<p>Hemolytic effect of nanospheres (<b>A</b>) and micelles (<b>B</b>) (* vs. C+, ±SD, <span class="html-italic">n</span> = 3).</p>
Full article ">Figure 5
<p>The effect of the drug-free nanospheres and micelles on the viability of L-929 cells (the results are shown as mean ± SD; <span class="html-italic">p</span> &lt; 0.05 compared with control).</p>
Full article ">Figure 6
<p>The effect of native compounds (<b>A</b>), compounds loaded into nanospheres (<b>B</b>) and compounds loaded into micelles (<b>C</b>) on the viability of HeLa cells, determined by means of a CCK-8 assay (the results are shown as mean ± SD; * <span class="html-italic">p</span> &lt; 0.05 compared with control).</p>
Full article ">Figure 7
<p>The effect of the 3d compound loaded into micelles (<b>A</b>) and drug-free micelles (<b>B</b>) on the viability of HeLa cells, analyzed by means of an SRB assay (the results are shown as mean ± SD; * <span class="html-italic">p</span> &lt; 0.05 compared with control).</p>
Full article ">Figure 8
<p>The effect of M/3d on LDH release from HeLa cells (the results are shown as mean ± SD; * <span class="html-italic">p</span> &lt; 0.05 compared with control).</p>
Full article ">Figure 9
<p>The effect of the 3d compound loaded into micelles (<b>A</b>) and drug-free micelles (<b>B</b>) on the proliferation of HeLa cells, determined by means of a BrdU assay (the results are shown as mean ± SD; * <span class="html-italic">p</span> &lt; 0.05 compared with control).</p>
Full article ">Scheme 1
<p>Synthesis of 5-methyl-12<span class="html-italic">H</span>-quino[3,4-<span class="html-italic">b</span>][1,4]benzothiazinium chlorides <b>3a</b>–<b>d</b>.</p>
Full article ">
26 pages, 1967 KiB  
Review
A Comprehensive Review: Mesoporous Silica Nanoparticles Greatly Improve Pharmacological Effectiveness of Phytoconstituent in Plant Extracts
by Diah Lia Aulifa, Bunga Amarilis, Luthfia Nur Ichsani, Devita Salsa Maharani, Ayunda Myela Shabrina, Hanifah Hanifah, Rizky Prasiska Wulandari, Agus Rusdin, Laila Subra and Arif Budiman
Pharmaceuticals 2024, 17(12), 1684; https://doi.org/10.3390/ph17121684 - 13 Dec 2024
Viewed by 459
Abstract
Medicinal plants are increasingly being explored due to their possible pharmacological properties and minimal adverse effects. However, low bioavailability and stability often limit efficacy, necessitating high oral doses to achieve therapeutic levels in the bloodstream. Mesoporous silica nanoparticles (MSNs) offer a potential solution [...] Read more.
Medicinal plants are increasingly being explored due to their possible pharmacological properties and minimal adverse effects. However, low bioavailability and stability often limit efficacy, necessitating high oral doses to achieve therapeutic levels in the bloodstream. Mesoporous silica nanoparticles (MSNs) offer a potential solution to these limitations. Due to their large surface area, substantial pore volume, and ability to precisely control pore size. MSNs are also capable of efficiently incorporating a wide range of therapeutic substances, including herbal plant extracts, leading to potential use for drug containment and delivery systems. Therefore, this review aimed to discuss and summarize the successful developments of herbal plant extracts loaded into MSN, focusing on preparation, characterization, and the impact on efficacy. Data were collected from publications on Scopus, PubMed, and Google Scholar databases using the precise keywords “mesoporous silica nanoparticle” and “herbal extract”. The results showed that improved phytoconstituent bioavailability, modified release profiles, increased stability, reduced dose and toxicity are the primary benefits of this method. This review offers insights on the significance of integrating MSNs into therapeutic formulations to improve pharmacological characteristics and effectiveness of medicinal plant extracts. Future prospects show favorable potential for therapeutic applications using MSNs combined with herbal medicines for clinical therapy. Full article
(This article belongs to the Section Pharmaceutical Technology)
Show Figures

Figure 1

Figure 1
<p>Flowchart of methodology.</p>
Full article ">Figure 2
<p>Overlay of DSC thermograms of E. arvense extract and this extract loaded into pSi. Adapted from data presented originally in Ref. [<a href="#B6-pharmaceuticals-17-01684" class="html-bibr">6</a>].</p>
Full article ">Figure 3
<p>XRD analysis of E. arvense dry extract, before and after loading into pSi microparticles. Adapted from data presented originally in Ref. [<a href="#B6-pharmaceuticals-17-01684" class="html-bibr">6</a>].</p>
Full article ">Figure 4
<p>The characterization of grape seed extract loaded into MSNs (GSE/MSN). Adapted from data presented originally in Ref. [<a href="#B52-pharmaceuticals-17-01684" class="html-bibr">52</a>].</p>
Full article ">Figure 5
<p>Mechanism of MSNs.</p>
Full article ">
11 pages, 2590 KiB  
Article
Biosynthesis, Characterization, and Antibacterial Activity of Gold, Silver, and Bimetallic Nanoparticles Using Annona squamosa L. Leaves
by Fatima Jibrin, Olufunto T. Fanoro, Rodney Maluleke, Thabang C. Lebepe, Nande Mgedle, Gracia It Mwad Mbaz, Olanrewaju A. Aladesuyi, Rajendran Kalimuthu, Oluwatoyin A. Odeku and Oluwatobi S. Oluwafemi
Antibiotics 2024, 13(12), 1199; https://doi.org/10.3390/antibiotics13121199 - 9 Dec 2024
Viewed by 567
Abstract
The utilization of nano-sized drug delivery systems in herbal drug delivery systems has a promising future for improving drug effectiveness and overcoming issues connected with herbal medicine. As a consequence, the use of nanocarriers as novel drug delivery systems for the improvement of [...] Read more.
The utilization of nano-sized drug delivery systems in herbal drug delivery systems has a promising future for improving drug effectiveness and overcoming issues connected with herbal medicine. As a consequence, the use of nanocarriers as novel drug delivery systems for the improvement of traditional medicine is critical to combating infectious diseases globally. In line with this, we herein report the biosynthesis of silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), and bimetallic nanoparticles (BMNPs) as antibacterial agents against pathogenic bacterial strains using Annona squamosa L. leaf extract as a bio-reductant and bio-stabilizing agent. The as-synthesized metal nanoparticles were characterized by transmission electron microscopy (TEM), ultraviolet–visible (UV–Vis) absorption spectroscopy, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and the dynamic light scattering (DLS) method. The as-synthesized MNPs had an average particle size of 6.98 nm ± 2.86 nm (AgNPs), 21.84 ± 8.72 nm (AuNPs), and 2.05 nm ± 0.76 nm (BMNPs). The as-synthesized AgNPs and BMNPs showed good antibacterial activity against pathogenic bacterial strains of Gram-positive Staphylococcus aureus (ATCC 25923) and Gram-negative Escherichia coli (ATCC 25922). The obtained results offer insight into the development of benign nanoparticles as safe antibacterial agents for antibiotic therapy using Annona squamosa L. leaf extract. Full article
Show Figures

Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Photographic image of (<b>A</b>(<b>i</b>)) AgNPs, (<b>A</b>(<b>ii</b>)) AuNPs, and (<b>A</b>(<b>iii</b>)) BMNPs biosynthesized from <span class="html-italic">A. squamosa</span> L. extract. (<b>B</b>) Absorption spectra of AgNPs synthesized using the aqueous extract of AS at ratios of 1:5 and 1:10. (<b>C</b>) Absorption spectra of AuNPs synthesized using the aqueous extract of AS. (<b>D</b>) Absorbance spectra of BMNPs_AS.</p>
Full article ">Figure 2
<p>(<b>A</b>) TEM micrograph of AgNPs_AS 1:5. (<b>B</b>) AgNP particle size distribution. (<b>C</b>) TEM micrograph of AuNPs_AS. (<b>D</b>) AuNP particle size distribution. (<b>E</b>) TEM micrograph of BMNPs. (<b>F</b>) BMNP particle size distribution.</p>
Full article ">Figure 3
<p>FTIR spectra of the AS extract and the as-synthesized MNPs using the aqueous extract of AS.</p>
Full article ">Figure 4
<p>XRD pattern of AgNPs, AuNPs, and BMNPs synthesized using aqueous extract of AS.</p>
Full article ">
28 pages, 2888 KiB  
Review
Nanotechnology-Based Approaches for the Management of Diabetes Mellitus: An Innovative Solution to Long-Lasting Challenges in Antidiabetic Drug Delivery
by Shounak Sarkhel, Saikat Mollick Shuvo, Md Ahesan Ansari, Sourav Mondal, Pritam Kapat, Arindam Ghosh, Tanima Sarkar, Ranu Biswas, Leonard Ionut Atanase and Alexandru Carauleanu
Pharmaceutics 2024, 16(12), 1572; https://doi.org/10.3390/pharmaceutics16121572 - 9 Dec 2024
Viewed by 604
Abstract
Diabetes is a widespread metabolic illness. Mismanagement of diabetes can lead to severe complications that tremendously impact patients’ quality of life. The assimilation of nanotechnology in diabetes care holds the potential to revolutionize treatment paradigms, improve patient outcomes, and reduce the economic burden [...] Read more.
Diabetes is a widespread metabolic illness. Mismanagement of diabetes can lead to severe complications that tremendously impact patients’ quality of life. The assimilation of nanotechnology in diabetes care holds the potential to revolutionize treatment paradigms, improve patient outcomes, and reduce the economic burden associated with this pervasive disease. This manuscript explores the multifaceted utilization of nanomaterials in diabetes care, emphasizing the unique features of nano-based medication delivery methods and smart drug delivery mechanisms. Additionally, this paper talks about research on nanocarrier-integrated oral, transdermal, and inhalable insulin delivery; dendrimer- and nanocarrier-coupled antisense oligonucleotide-driven gene therapy; the implementation of gold nanoparticles and quantum dots for glucose surveillance; and nucleic acid therapies. There are certain restrictions when using medication delivery methods that are commonly available to handle diabetes. In order to increase efficacy and safety, the rapidly developing science of nanotechnology is also being explored and employed in medical biology. Nanomaterials like liposomes, dendrimers, niosomes, polymeric and metallic nanocarriers, and solid lipid nanoparticles are among the nanocarriers that have been developed for better delivery of various oral hypoglycemic agents in comparison to conventional therapies. These nanocarriers provide great control over elevated blood glucose levels, making them one of the most intriguing and promising technologies available today. Furthermore, adding additional ligands to nanocarriers allows for more focused distribution while protecting the encapsulated hypoglycemic drugs. Full article
Show Figures

Figure 1

Figure 1
<p>Nanotechnology-based approaches to address challenges associated with traditional therapy. (<b>A</b>) Numerous benefits of implementation of nanotechnology in diabetes treatment compared to conventional treatment procedure(drawn by authors). (<b>B</b>) Illustration of liposomal vs. non-liposomal antidiabetic drug delivery based on permeability. Here, red “X” indication to show the fact that non-liposomal antidiabetic medications are unable to permeate through the cell membrane. Since the liposomal system is permeable, the encapsulated antidiabetic medications can potentially be transported to the target cells with greater efficiency [<a href="#B31-pharmaceutics-16-01572" class="html-bibr">31</a>].</p>
Full article ">Figure 2
<p>(<b>A</b>)Emerging nanomaterials/nanocarriers for treatment and regulation of diabetes mellitus [<a href="#B32-pharmaceutics-16-01572" class="html-bibr">32</a>]. (<b>B</b>)Flow prism of nanomaterials for diabetes mellitus (drawn by authors).</p>
Full article ">
15 pages, 3170 KiB  
Article
Preparation and Characterization of Small-Size and Strong Antioxidant Nanocarriers to Enhance the Stability and Bioactivity of Curcumin
by Shanshan Tie, Yujin Yang, Jiawei Ding, Yanyan Li, Mengmeng Xue, Jianrui Sun, Fang Li, Qiuxia Fan, Ying Wu and Shaobin Gu
Foods 2024, 13(23), 3958; https://doi.org/10.3390/foods13233958 - 8 Dec 2024
Viewed by 551
Abstract
The purpose of this study was to design nanocarriers with small-size and antioxidant properties for the effective encapsulation of curcumin. Here, procyanidins, vanillin, and amino acids were used to successfully prepare nanocarriers of a controllable size in the range of 328~953 nm and [...] Read more.
The purpose of this study was to design nanocarriers with small-size and antioxidant properties for the effective encapsulation of curcumin. Here, procyanidins, vanillin, and amino acids were used to successfully prepare nanocarriers of a controllable size in the range of 328~953 nm and to endow antioxidant ability based on a one-step self-assembly method. The reaction involved a Mannich reaction on the phenolic hydroxyl groups of procyanidins, aldehyde groups of vanillin, and amino groups of amino acids. Subsequently, curcumin nanoparticles were prepared by loading curcumin with this nanocarrier, and the encapsulation efficiency of curcumin was 85.97%. Compared with free curcumin, the antioxidant capacity and photothermal stability of the embedded curcumin were significantly improved, and it could be slowly released into simulated digestive fluid. Moreover, using the corticosterone-induced PC12 cell injury model, the cell viability increased by 23.77% after the intervention of curcumin nanoparticles, and the cellular antioxidant capacity was also significantly improved. The nanoparticles prepared in this work can effectively improve the solubility, stability, and bioactivity of curcumin, which provides a reference for the embedding and delivery of other hydrophobic bioactive compounds. Full article
(This article belongs to the Section Food Nutrition)
Show Figures

Figure 1

Figure 1
<p>Preparation and particle size characterization of nanocarriers. (<b>a</b>) A schematic diagram of the preparation of NCs−1~NCs−8 using PCs, vanillin, and amino acids as raw materials. (<b>b</b>) Particle size, polydispersity index (PDI), and (<b>c</b>) particle size distribution of amino acid-dependent nanocarriers NCs−1~NCs−3. (<b>d</b>) Particle size, PDI, and (<b>e</b>) particle size distribution of PC-dependent nanocarriers NCs−1 and NCs−4~NCs−5. (<b>f</b>) Particle size, PDI, and (<b>g</b>) particle size distribution of vanillin-dependent nanocarriers NCs−1 and NCs−6~NCs−8. Note: the lower letters a, b, and c indicate that there are statistically significant differences between the samples.</p>
Full article ">Figure 2
<p>Formation and spectral characterization. (<b>a</b>) Schematic illustration of the reaction pathway of NCs. FTIR spectra of (<b>b</b>) vanillin (Van), Lys, (<b>c</b>) PCs, and NCs. (<b>d</b>) UV-Vis spectra and (<b>e</b>) crystal structure of PCs and NCs.</p>
Full article ">Figure 3
<p>Preparation and characterization of Cur NPs. (<b>a</b>) A schematic diagram of preparation, SEM image, and (<b>b</b>) embedding efficiency (EE) of Cur NPs. (<b>c</b>) FTIR spectra, (<b>d</b>) UV−vis spectra and (<b>e</b>) crystal structure of Cur NPs.</p>
Full article ">Figure 4
<p>Antioxidant capacity experiment. (<b>a</b>) DPPH and (<b>b</b>) ABTS radical scavenging activities for Cur, NCs, and Cur NPs. Note: the lower letters a, b, and c indicate that there are statistically significant differences between the samples.</p>
Full article ">Figure 5
<p>(<b>a</b>) UV irradiation and (<b>b</b>) thermal stability analyses for Cur and Cur NPs. Note: the lower letters a, b, and indicate that there are statistically significant differences between the samples.</p>
Full article ">Figure 6
<p>(<b>a</b>) Schematic diagram of simulated digestion and (<b>b</b>) release profile of Cur NPs.</p>
Full article ">Figure 7
<p>Cell viability analysis. (<b>a</b>) The effect of different concentrations of CORT on the viability of PC12 cells. Effect of (<b>b</b>) NCs, (<b>c</b>) Cur, and (<b>d</b>) Cur NPs on the cell viability of 400 μM CORT-induced PC12 cells. Note: the lower letters a−e indicate that there are statistically significant differences between the samples.</p>
Full article ">Figure 8
<p>Effect of Cur, NCs, and Cur NPs on the levels of (<b>a</b>) T-SOD, (<b>b</b>) CAT, and (<b>c</b>) MDA in PC12 cells induced by CORT. Note: the lower letters a, b, c, and d indicate that there are statistically significant differences between the samples.</p>
Full article ">Figure 9
<p>(<b>a</b>) Optical images of Cur NPs and NCs. (<b>b</b>) Optical images and hemolysis rate (HR) of negative control, positive control, Cur NPs, and NCs after treatment of red blood cells.</p>
Full article ">
25 pages, 2777 KiB  
Review
Why Extracellular Vesicles Are Attractive Vehicles for RNA-Based Therapies?
by Farah Aqel, Kristin Schneider, Denise Hartung, Kathrin Schwarz and Olga Shatnyeva
SynBio 2024, 2(4), 378-402; https://doi.org/10.3390/synbio2040024 - 5 Dec 2024
Viewed by 832
Abstract
Extracellular Vesicles (EVs) are a focus of intense research worldwide, with many groups exploring their potential for both diagnostic and therapeutic applications. Researchers have characterized EVs into various subtypes, modified common surface markers, and developed diverse isolation and purification techniques. Beyond their diagnostic [...] Read more.
Extracellular Vesicles (EVs) are a focus of intense research worldwide, with many groups exploring their potential for both diagnostic and therapeutic applications. Researchers have characterized EVs into various subtypes, modified common surface markers, and developed diverse isolation and purification techniques. Beyond their diagnostic potential, EVs are being engineered as delivery vehicles for various molecules and therapeutics. RNA therapeutics have the potential to be a transformative solution for patients suffering from chronic and genetic disorders and generally targeting undruggable targets. Despite the success of many RNA therapeutics in both in vivo studies and clinical trials, a significant challenge remains in effectively delivering these therapies to the target cells. Many research groups have adopted the use of lipid nanoparticles (LNPs) and other nanocarriers to encapsulate RNA therapeutics, aiming to deliver them as stably as possible to ensure optimal bioavailability and efficacy. While LNPs have proven successful as delivery vehicles, their use is not without drawbacks, such as accumulation within the body. EVs could be a potential solution to many of the problems around LNPs and other nanocarriers. Full article
Show Figures

Figure 1

Figure 1
<p>Biogenesis of extracellular vesicles and apoptotic bodies. (<b>A</b>). Exosomes are formed by fusing the multivesicular body with the plasma membrane and releasing them into the extracellular space. Microvesicles bud from the plasma membrane. (<b>B</b>). Dying cells release apoptotic bodies and apoptotic microvesicles.</p>
Full article ">Figure 2
<p>EVs’ composition. EVs contain various transmembrane molecules, which include tetraspanins (e.g., CD63, CD9, and CD81), MHC molecules (I and II), integrins, ligands (e.g., PD-L1), receptors (e.g., EGFR, TNFR), and proteoglycans. Luminal substances include DNA, RNA, proteins (e.g., enzymes, ALIX), cytoskeletal proteins (e.g., actin, tubulin), and metabolites (e.g., sugars, fatty acids).</p>
Full article ">Figure 3
<p>Heatmap displaying the advantages and disadvantages of extracellular vesicle isolation methods based on purity, yield, concentration, throughput, scalability, cost of production, and required time.</p>
Full article ">Figure 4
<p>Extracellular vesicle isolation and purification methods (<b>A</b>). Differential centrifugation: (2) Live and dead cells as well as debris are sedimented out of the cell culture medium at increasing centrifugal speeds. (3) The cell culture medium then undergoes either UC at 100,000 g or is layered on top of a sucrose gradient and then centrifuged at 100,000 g (<b>B</b>). Immunocapturing: EVs are incubated with magnetic beads carrying antibodies against certain EV markers; the suspension is then added to a column placed on a magnet where the beads binding to EVs are captured and everything else is eluted; EVs are isolated when the column is removed from the magnet (<b>C</b>). Size Exclusion Chromatography (SEC): EVs and other small substances will enter the pores; larger particles will elute first, and smaller particles will be eluted in later fractions (<b>D</b>). Ultrafiltration: When centrifugal force is applied, the EVs pass through the filter, and the larger particles are retained (<b>E</b>). Polymer precipitation: non-water-soluble particles, such as EVs, will be expelled out of solution and sediment as a hydrophilic polymer binds water-soluble substances. The sediment can then be collected by centrifuging at low speed (<b>F</b>). Anion Exchange Chromatography (AEX): As the sample is applied to the column, the negatively charged EVs will bind the positively charged matrix while other substances are eluted. For sample collection, the EVs are desorbed from the matrix by changing the ionic strength of the buffer. Figure adapted from “Extracellular Vesicle Separation by Density Gradient Ultracentrifugation”, “Chromatography 2 (Layout)”, and “Anion and Cation Exchange Chromatography” using <a href="http://BioRender.com" target="_blank">BioRender.com</a> (2022). Retrieved from <a href="https://app.biorender.com/biorender-templates" target="_blank">https://app.biorender.com/biorender-templates</a>. Accessed on 17 January 2023.</p>
Full article ">Figure 5
<p>Extracellular vesicles post-isolation modification methods. Interior modifications: (<b>A</b>). EVs are co-incubated with cargo that passively diffuses into the EVs. (<b>B</b>). In electroporation, sonication, and freeze–thaw techniques, the membrane of the EVs is physically disrupted; cargo is then expected to diffuse into EVs through pores. (<b>C</b>). With the extrusion method, the membrane is disrupted by pushing the particles and the cargo through a porous membrane. (<b>D</b>). Chemical transfection method employs a surfactant to load the EVs. Surface Modification: (<b>E</b>). EVs can be incorporated with polyethylene glycol (PEG) by incubating them with PEGylated micelles.</p>
Full article ">Figure 6
<p>Pros and cons of extracellular vesicles, lipid nanoparticles, and hybridosomes as targeted drug delivery vehicles.</p>
Full article ">
19 pages, 932 KiB  
Review
Polycystic Ovary Syndrome and the Potential for Nanomaterial-Based Drug Delivery in Therapy of This Disease
by Mingqin Shi, Xinyao Li, Liwei Xing, Zhenmin Li, Sitong Zhou, Zihui Wang, Xuelian Zou, Yuqing She, Rong Zhao and Dongdong Qin
Pharmaceutics 2024, 16(12), 1556; https://doi.org/10.3390/pharmaceutics16121556 - 4 Dec 2024
Viewed by 685
Abstract
Polycystic ovary syndrome (PCOS) is the predominant endocrine disorder among women of reproductive age and represents the leading cause of anovulatory infertility, which imposes a considerable health and economic burden. Currently, medications used to treat PCOS can lead to certain adverse reactions, such [...] Read more.
Polycystic ovary syndrome (PCOS) is the predominant endocrine disorder among women of reproductive age and represents the leading cause of anovulatory infertility, which imposes a considerable health and economic burden. Currently, medications used to treat PCOS can lead to certain adverse reactions, such as affecting fertility and increasing the risk of venous thrombosis. Drug delivery systems utilizing nanomaterials, characterized by prolonged half-life, precision-targeted delivery, enhanced bioavailability, and reduced toxicity, are currently being employed in the management of PCOS. This innovative approach is gaining traction as a favored strategy for augmenting the therapeutic efficacy of medications. Consequently, this paper discusses the roles of nanoparticles, nanocarriers, and targeted ligands within nanomaterial-based drug delivery systems, aiming to identify optimal methodologies for treating PCOS using nanomaterials. Additionally, prospective research avenues concerning nanomaterial-based delivery systems in the context of PCOS, as well as the implications of existing insights on the advancement of novel therapies for PCOS, are highlighted. Full article
(This article belongs to the Special Issue New Technology for Prolonged Drug Release, 2nd Edition)
Show Figures

Figure 1

Figure 1
<p>Nanomaterials and targeted ligands in PCOS therapy. (<b>A</b>) The pathophysiological mechanisms underlying polycystic ovary syndrome (PCOS) predominantly encompass hyperandrogenism, insulin resistance, inflammatory responses, and oxidative stress. Current therapeutic approaches for PCOS primarily consist of pharmacological interventions, lifestyle modifications, and psychotherapy. (<b>B</b>) A diverse array of novel nanomaterials has been employed for the management of PCOS. This includes nanoparticles—natural medicine nanoparticles sourced from ginger, cinnamon, camellia, and aloe vera, as well as metal-based nanoparticles derived from silver, iron, and selenium—along with liposomes, nanotubes, quantum dots, and micelles. (<b>C</b>) Oocytes and granulosa cells may serve as targeted ligands, playing a significant role in innovative drug delivery systems. Chitosan and mannose can provide a protective function for the ovaries by binding to oocytes. Moreover, copper and silver nanoparticles possess the capability to transit through granulated cells, thereby influencing ovarian functions.</p>
Full article ">
24 pages, 3171 KiB  
Review
Innovative Nanomedicine Delivery: Targeting Tumor Microenvironment to Defeat Drug Resistance
by Wenjun Meng, Li Huang, Jiamin Guo, Qing Xin, Jiyan Liu and Yuzhu Hu
Pharmaceutics 2024, 16(12), 1549; https://doi.org/10.3390/pharmaceutics16121549 - 3 Dec 2024
Viewed by 576
Abstract
Nanodrug delivery systems have revolutionized tumor therapy like never before. By overcoming the complexity of the tumor microenvironment (TME) and bypassing drug resistance mechanisms, nanotechnology has shown great potential to improve drug efficacy and reduce toxic side effects. This review examines the impact [...] Read more.
Nanodrug delivery systems have revolutionized tumor therapy like never before. By overcoming the complexity of the tumor microenvironment (TME) and bypassing drug resistance mechanisms, nanotechnology has shown great potential to improve drug efficacy and reduce toxic side effects. This review examines the impact of the TME on drug resistance and recent advances in nanomedicine delivery systems to overcome this challenge. Characteristics of the TME such as hypoxia, acidity, and high interstitial pressure significantly reduce the effectiveness of chemotherapy and radiotherapy, leading to increased drug resistance in tumor cells. Then, this review summarizes innovative nanocarrier designs for these microenvironmental features, including hypoxia-sensitive nanoparticles, pH-responsive carriers, and multifunctional nanosystems that enable targeted drug release and improved drug penetration and accumulation in tumors. By combining nanotechnology with therapeutic strategies, this review offers a novel perspective by focusing on the innovative design of nanocarriers that interact with the TME, a dimension often overlooked in similar reviews. We highlight the dual role of these nanocarriers in therapeutic delivery and TME modulation, emphasize their potential to overcome drug resistance, and look at future research directions. Full article
Show Figures

Figure 1

Figure 1
<p>Composition of the TME. The TME consists of a variety of cellular and non-cellular components, including tumor-associated fibroblasts (CAFs); immune cells such as macrophages, T cells, natural killer cells, and endothelial cells; pericytes; the extracellular matrix (ECM); and growth factors and cytokines. Created with BioRender.com.</p>
Full article ">Figure 2
<p>Schematic diagram of nanomaterials employed to diagnose and treat cancers, including nanodiamonds, mesoporous silica, metal nanoparticles (MNPs), liposomes, quantum dots (QDs), polymeric NPs, micelles, and dendrimers. Created with BioRender.com.</p>
Full article ">Figure 3
<p>The p-nitrobenzyl groups in mPEG-PLG-NC are supposed to be reduced to p-aminobenzyl groups by overexpressed nitroreductase in hypoxic cells and undergo spontaneous fragmentation via 1,6-elimination, resulting in hypoxiaresponsive drug release. (Reprinted with permission from [<a href="#B58-pharmaceutics-16-01549" class="html-bibr">58</a>]. Copyright 2020 American Chemical Society).</p>
Full article ">Figure 4
<p>Acidic pH-responsive poly(lactide-co-glycolide) (PLGA) nanoparticles for the endo-lysosome-specific release of 522, a novel TLR7/8 agonist. Bicarbonate salt was incorporated into the new formulation to generate carbon dioxide (CO<sub>2</sub>) gas at acidic pH, which can disrupt the polymer shell to rapidly release the payload, and the polymer shell can be used for the release of the payload. (Reprinted with permission from [<a href="#B71-pharmaceutics-16-01549" class="html-bibr">71</a>]. Copyright 2018 Royal Society of Chemistry).</p>
Full article ">Figure 5
<p>Nanocarrier strategies to overcome tumor drug resistance. Tumor drug resistance mediated by ATP-binding cassette (ABC) transporters is addressed through two strategies: reversal and bypass. Traditional chemotherapy drugs are effluxed by ABC transporters, reducing efficacy (<b>top left</b>). Reversal involves nanocarriers co-delivering drugs and transporter inhibitors to block efflux and restore drug sensitivity (<b>top right</b>). The bypass strategy uses drug-encapsulated nanoparticles to avoid transporter recognition, enabling intracellular drug release after uptake (<b>bottom right</b>), improving efficacy compared to unencapsulated drugs (<b>bottom left</b>). Created with BioRender.com.</p>
Full article ">Figure 6
<p>Mechanism of pH-responsive polymer nanomaterials for tumor-targeted drug delivery. Anti-tumor drugs are encapsulated into pH-responsive polymer nanomaterials through a drug-loading process. In normal tissues (pH = 7.4), the nanomaterials remain stable, minimizing premature drug release. Upon reaching the acidic tumor microenvironment (pH &lt; 6.5), the pH-responsive polymers degrade, triggering the controlled release of the encapsulated drugs. This mechanism enhances drug delivery efficiency to tumor cells while reducing off-target effects in normal tissues. Created with BioRender.com.</p>
Full article ">
22 pages, 6113 KiB  
Article
Laponite vs. Montmorillonite as Eugenol Nanocarriers for Low Density Polyethylene Active Packaging Films
by Achilleas Kechagias, Constantinos E. Salmas, Nikolaos Chalmpes, Areti A. Leontiou, Michael A. Karakassides, Emmanuel P. Giannelis and Aris E. Giannakas
Nanomaterials 2024, 14(23), 1938; https://doi.org/10.3390/nano14231938 - 2 Dec 2024
Viewed by 797
Abstract
Although a lot of recent research revealed advantages of novel biopolymers’ implementation as active food packaging polymers, there is not an equivalent effort from industry to use such films, probably because of the required cost to change the supply chain and the equipment. [...] Read more.
Although a lot of recent research revealed advantages of novel biopolymers’ implementation as active food packaging polymers, there is not an equivalent effort from industry to use such films, probably because of the required cost to change the supply chain and the equipment. This study investigates the use of two natural abundant nanoclays, laponite (Lap) and montmorillonite (Mt), as eugenol slow-release carriers for enhancing the functionality of low-density polyethylene (LDPE) active packaging films. The target is to combine the spirit of the circular economy with the existent technology and the broadly used materials to develop a novel attractive product for active food packaging applications. Utilizing a vacuum-assisted adsorption method, eugenol was successfully intercalated into Lap and Mt nanoclays, forming EG@Lap and EG@Mt nanohybrids. Testing results confirmed effective integration and dispersion of the nanohybrids within the LDPE matrix. The most promising final film seems to be the LDPE with 15% w/w EG@Lap nanohybrid which exhibited a higher release rate (k2 = 5.29 × 10−4 s−1) for temperatures ≤70 °C, similar mechanical properties, a significantly improved water barrier (Dwv = 11.7 × 10−5 cm2·s−1), and a slightly improved oxygen barrier (PeO2 = 2.03 × 10−8 cm2·s−1) compared with neat LDPE. Antimicrobial and sensory tests on fresh minced pork showed two days’ shelf-life extension compared to pure LDPE and one more day compared to LDPE with 15% w/w EG@Mt nanohybrid. Full article
(This article belongs to the Special Issue Antimicrobial and Antioxidant Activity of Nanoparticles)
Show Figures

Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Schematic presentation (<b>left</b> part) and image (<b>right</b> part) of handmade apparatus used for the preparation of the EG@Lap and EG@Mt nanohybrids: (1) stirrer with a heating plate, (2) spherical glass flask, (3) security valve of the pump, (4) security valve of the CV tank, (5) air vacuum pump, and (6) CV tank. CV: carvacrol and NZ: natural zeolite.</p>
Full article ">Figure 2
<p>(<b>a</b>) XRD plots of (1) pure Lap, (2) dried Lap, and (3) EG@Lap nanohybrid; (<b>b</b>) XRD plots of (1) pure Mt, (2) dried Mt, and (3) EG@Mt nanohybrid.</p>
Full article ">Figure 3
<p>EG desorption isotherm kinetic plots (in triplicates) for EG@Lap (<b>left</b> part (<b>a</b>–<b>c</b>) plots) and EG@Mt (<b>right</b> part (<b>d</b>–<b>f</b>) plots) nanohybrids at 70 °C ((<b>a</b>,<b>d</b>) plots), 90 °C ((<b>b</b>,<b>e</b>) plots), and 110 °C ((<b>c</b>,<b>f</b>) plots). The red line shows the simulation plots according to the pseudo-second-order kinetic model.</p>
Full article ">Figure 4
<p>Plot of ln(1/k<sub>2</sub>) values as a function of (1/T) for both EG@Lap and EG@Mt nanohybrids.</p>
Full article ">Figure 5
<p>Representative SEM images of (<b>a</b>) pure Lap, (<b>b</b>) pure Mt, (<b>c</b>) EG@Lap, and (<b>d</b>) EG@Mt.</p>
Full article ">Figure 6
<p>(<b>a</b>) XRD plots of (1) pure LDPE film, (2) LDPE/5EG@Lap active film, (3) LDPE/10EG@Lap active film, and (4) LDPE/15EG@Lap active film; (<b>b</b>) XRD plots of (1) pure LDPE film, (2) LDPE/5EG@Mt active film, (3) LDPE/10EG@Mt active film, and (4) LDPE/15EG@Mt active film.</p>
Full article ">Figure 7
<p>SEM images of (<b>a</b>) LDPE/5EG@Lap, (<b>b</b>) LDPE/10EG@Lap, (<b>c</b>) LDPE/15EG@Lap, (<b>d</b>) LDPE/5EG@Mt, (<b>e</b>) LDPE/10EG@Mt, and (<b>f</b>) LDPE/15EG@Mt active films.</p>
Full article ">Figure 8
<p>Stress-strain curves for (1) black line, LDPE, (2) blue line, LDPE/5EG@Lap, (3) green line, LDPE/10EG@Lap, (4) red line, LDPE/15EG@Lap, (5) dashed blue line, LDPE/5EG@Mt, (6) dashed green line, LDPE/10EG@Mt, and (7) dashed red line, LDPE/15EG@Mt.</p>
Full article ">Figure 9
<p>EG desorption isotherm kinetic plots (in triplicates) for all LDPE/xEG@Lap (<b>left</b> part (<b>a</b>–<b>c</b>) plots) and all LDPE/xEG@Mt (<b>right</b> part (<b>d</b>–<b>f</b>) plots) nanohybrids at 70 °C. The red line shows the simulation plots according to the pseudo-second-order kinetic model.</p>
Full article ">
Back to TopTop