Docetaxel-Loaded Chitosan-Cholesterol Conjugate-Based Self-Assembled Nanoparticles for Overcoming Multidrug Resistance in Cancer Cells

Mu, Chaofeng; Cui, Fude; Yin, Yongmei; Cho, Hyun‐Jong; Kim, Dae-Duk

doi:10.3390/pharmaceutics12090783

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…Furthermore, the C–O–C bond present at 695 cm −1 denoted the interaction between DTX and CS, 26 while the interaction between CH and DOXO is present by a N–C=O bond at 1580 cm −1 (Refs. 27 and 28 ) in Figs. 1(b) and S3.…”

Section: Resultsmentioning

confidence: 98%

Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma

Desmond,

Margini,

Barchiesi

et al. 2024

APL Bioengineering

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Osteosarcoma (OS) is a rare form of primary bone cancer, impacting approximately 3.4 × 106 individuals worldwide each year, primarily afflicting children. Given the limitations of existing cancer therapies, the emergence of nanotheranostic platforms has generated considerable research interest in recent decades. These platforms seamlessly integrate therapeutic potential of drug compounds with the diagnostic capabilities of imaging probes within a single construct. This innovation has opened avenues for enhanced drug delivery to targeted sites while concurrently enabling real-time monitoring of the vehicle's trajectory. In this study, we developed a nanotheranostic system employing the layer-by-layer (LbL) technique on a core containing doxorubicin (DOXO) and in-house synthesized carbon quantum dots. By utilizing chitosan and chondroitin sulfate as polyelectrolytes, we constructed a multilayered coating to encapsulate DOXO and docetaxel, achieving a coordinated co-delivery of both drugs. The LbL-functionalized nanoparticles exhibited an approximate size of 150 nm, manifesting a predominantly uniform and spherical morphology, with an encapsulation efficiency of 48% for both drugs. The presence of seven layers in these systems facilitated controlled drug release over time, as evidenced by in vitro release tests. Finally, the impact of the LbL-functionalized nanoparticles was evaluated on U2OS and Saos-2 osteosarcoma cells. The synergistic effect of the two drugs was found to be crucial in inducing cell death, particularly in Saos-2 cells treated with nanoparticles at concentrations higher than 10 μg/ml. Transmission electron microscopy analysis confirmed the internalization of the nanoparticles into both cell types through endocytic mechanisms, revealing an underlying mechanism of necrosis-induced cell death.

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Section: Resultsmentioning

confidence: 98%

Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma

Desmond,

Margini,

Barchiesi

et al. 2024

APL Bioengineering

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“…The average particle size of the NPs was less than 200 nm, with polydispersity indexes (PDI) values <0.2, indicating that the TMZ16e-NPs were well dispersed and suitable for intranasal administration. The TMZ16e-NPs and anti-EphA3-TMZ16e-NPs had zeta potentials of -23.05 ± 1.48 mV and -28.65 ± 1.20 mV, respectively, indicating NP stability ( Mu et al, 2020 ). The DL% of TMZ16e-NPs and anti-EphA3-TMZ16e-NPs were 17.13% and 16.81%, respectively, and the EE% was more than 90% for both NPs.…”

Section: Resultsmentioning

confidence: 99%

Temozolomide hexadecyl ester targeted plga nanoparticles for drug-resistant glioblastoma therapy via intranasal administration

Wang

Yu²,

Wang³

et al. 2022

Front. Pharmacol.

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Introduction: Temozolomide (TMZ) is the first-line drug for glioblastoma (GBM), but it is limited in clinical use due to the drug resistance, poor brain targeting, and side effects. Temozolomide hexadecyl ester (TMZ16e), a TMZ derivative with high lipophilicity, membrane permeability, and high anti-glioma properties, has the potential to reverse drug resistance. In this study, anti-ephrin type-A receptor 3 (EphA3) modified TMZ16e loaded nanoparticles (NPs) were prepared for targeted GBM therapy via intranasal administration to deliver TMZ16e to the brain, treat drug-resistant glioma effectively, and reduce peripheral toxicity.Methods: TMZ16e loaded NPs were prepared by emulsion solvent evaporation method followed by modified with anti-EphA3 (anti-EphA3-TMZ16e-NPs). In vitro evaluations were performed by an MTT assay and flow cytometry analysis. The orthotopic nude mice models were used to evaluate the anti-glioma effect in vivo. Additionally, we investigated the anti-drug resistant mechanism by western blot analysis.Results: The particle size of the prepared NPs was less than 200 nm, and the zeta potential of TMZ16e-NPs and anti-EphA3-TMZ16e-NPs were -23.05 ± 1.48 mV and -28.65 ± 1.20mV, respectively, which is suitable for nasal delivery. In vitro studies have shown that anti-EphA3 modification increased the cellular uptake of nanoparticles in T98G cells. The cytotoxicity in the anti-EphA3-TMZ16e-NPs treated group was significantly higher than that of the TMZ16e-NPs, TMZ16e, and TMZ groups (p < 0.01), and the cell cycle was blocked. Western blotting analysis showed that the TMZ16e-loaded NPs were able to effectively downregulate the expression level of O6-methylguanine-deoxyribonucleic acid-methyltransferase (MGMT) protein in T98G cells and reverse drug resistance. In vivo studies showed that the median survival time of tumor-bearing nude mice in the anti-EphA3-TMZ16e-NPs group was extended to 41 days, which was 1.71-fold higher than that of the saline group and the TUNEL staining results of the brain tissue section indicated that the TMZ16e-loaded NPs could elevate apoptosis in T98G cells.Conclusion: In conclusion, the TMZ16e-loaded NPs can be effectively delivered to the brain and targeted to gliomas, exhibiting better anti-glioma activity, indicating they possess great potential in the treatment of drug-resistant glioma.

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“…Docetaxel (DTX) is poorly soluble in water; thus, it requires solubilizers. This disadvantage could be overcome by cholesterol conjugation to chitosan to obtain an amphiphilic CS derivative [ 79 ]. The presence of a hydrophobic unit should facilitate the entrapment of a hydrophobic drug.…”

Section: Cs Np Platforms For a Specific Drug Deliverymentioning

confidence: 99%

Chitosan-Based Nanoparticles with Optimized Parameters for Targeted Delivery of a Specific Anticancer Drug—A Comprehensive Review

Kurczewska

2023

Pharmaceutics

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Chitosan is a positively charged polysaccharide obtained through chitin deacetylation. It belongs to a group of biodegradable, bioavailable, and non-toxic materials of natural origin; thus, it is a promising matrix for creating delivery systems of different active agents. Recently, much attention has been paid to nanodelivery systems as carriers to enable better bioavailability, and thus higher efficiency of the loaded drug. The present review is focused on the progress in chitosan-based nanoparticles for the targeted delivery of antitumor drugs. The paper discusses literature reports from the last three years in which chitosan nanoparticles were applied as carriers for active substances used in antitumor therapy and potential new drugs with anticancer properties. Special attention was paid to the different treatments applied to increase the therapeutic effectiveness and minimize the side effects of a specific active substance.

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Docetaxel-Loaded Chitosan-Cholesterol Conjugate-Based Self-Assembled Nanoparticles for Overcoming Multidrug Resistance in Cancer Cells

Cited by 7 publications

References 37 publications

Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma

Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma

Temozolomide hexadecyl ester targeted plga nanoparticles for drug-resistant glioblastoma therapy via intranasal administration

Chitosan-Based Nanoparticles with Optimized Parameters for Targeted Delivery of a Specific Anticancer Drug—A Comprehensive Review

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