Preparation and evaluation of reduction-responsive micelles based on disulfide-linked chondroitin sulfate A-tocopherol succinate for controlled antitumour drug release

Abstract

Objectives The study was to construct reduction-responsive chondroitin sulfate A (CSA)-conjugated TOS (CST) micelles with disulfide bond linkage, which was used for controlled doxorubicin (DOX) release and improved drug efficacy in vivo. Methods CST and non-responsive CSA-conjugated TOS (CAT) were synthesized, and the chemical structure was confirmed by Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, fluorescence spectrophotometer and dynamic light scattering. Antitumour drug DOX was physically encapsulated into CST and CSA by dialysis method. Cell uptake of DOX-based formulations was investigated by confocal laser scanning microscopy. In vitro cytotoxicity was studied in A549 and AGS cells. Furthermore, antitumour activity was evaluated in A549-bearing mice. Key findings CST and CAT can form self-assembled micelles, and have low value of critical micelle concentration. Notably, DOX-containing CST (D-CST) micelles demonstrated reduction-triggered drug release in glutathione-containing media. Further, reduction-responsive uptake of D-CST was observed in A549 cells. In addition, D-CST induced stronger cytotoxicity (P < 0.05) than DOX-loaded CAT (D-CAT) against A549 and AGS cells. Moreover, D-CST exhibited significantly stronger antitumour activity in A549-bearing nude mice than doxorubicin hydrochloride and D-CAT. Conclusions The reduction-responsive CST micelles enhanced the DOX effect at tumour site and controlled drug release.

Smart Chondroitin Sulfate Micelles for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Metastasis

“…As stated, the negative potentials were beneficial for passive targeting by the EPR effect and prevention of rapid clearance of the micelles in vivo. 17 …”

“…As stated, the negative potentials were beneficial for passive targeting by the EPR effect and prevention of rapid clearance of the micelles in vivo. 17 Amphiphilic copolymer could form self-assembled aggregates in aqueous media. By using a dialysis method, the DOX base was encapsulated into the core of CSSD or ACSSD micelles.…”

“…16 Chondroitin sulfate A (CSA) is a kind of natural and biodegradable materials, and its derivatives have been investigated and used as active targeting vehicles in CD44 receptor-overexpressed tumor cells. [17][18][19] Deoxycholic acid (DOCA) is a bile acid that can emulsify and solubilize dietary fats in our bodies. Then, both CSA and DOCA exhibit good biocompatibility.…”

Chondroitin Sulfate-Derived Paclitaxel Nanocrystal via π–π Stacking with Enhanced Stability and Tumor Targetability

“…Previously, CS-derived nanoscale micelles demonstrate excellent cellular uptake efficiency and Golgi-specific distribution in hepatic stellate cells or 4T1 breast cancer cells. , To further elucidate the impact of the nanocrystal shape on its cellular internalization behavior, CS-Fmoc-derived nanocrystals and micelles are subjected to a comparison study. DiD-labeled PTX NC@CS-Fmoc (denoted as DiD/PTX NC@CS-Fmoc) and CS-Fmoc micelles (denoted as DiD@CS-Fmoc) were synthesized in a similar way as compared to PTX NC@CS-Fmoc.…”

Multifunctional Nanoparticles Codelivering Doxorubicin and Amorphous Calcium Carbonate Preloaded with Indocyanine Green for Enhanced Chemo-Photothermal Cancer Therapy

“…The loading contents (LC) were calculated from the weight of encapsulating drug (DOX or ICG) divided by the amount of total drug-containing nanoparticles. 31 …”