Hybrid micelles based on Pt (IV) polymeric prodrug and TPGS for the enhanced cytotoxicity in drug-resistant lung cancer cells.

Colloids and Surfaces. B, Biointerfaces
Le HeRupei Tang

Abstract

Multidrug resistance (MDR) is a primary cause of failure in oncotherapy and interest is growing in the design of multi-stimuli responsive nano-carriers to synergistically deliver chemotherapeutic agents and P-gp inhibitors to reverse MDR. The hybrid micelles based on a Platinum (IV)-coordinate polymeric prodrugs and TPGS were developed to improve chemotherapy and reduce side effects. The pH/redox dual-sensitive polymers were synthesized by condensation polymerization using ortho ester monomer and diamminedichlorodisuccinatoplatinum (DSP). The hybrid micelles possessed uniform size (38 nm) and displayed good stability in various physiological conditions. In contrast, in vitro drug release profiles indicated that these micelles could be completely depolymerized under acidic and reducing environment, thereby more than 80 % cisplatin were released within 12 h at pH 5.0 plus 10 mM DTT. More importantly, a large amount of TPGS released simultaneously could effectively inhibit the function of drug efflux pumps, which significantly enhanced the cytotoxicity of cisplatin against A549/DDP cells. The growth inhibition rate of micelles on A549/DDP multicellular spheroids was 79.5 %, while that of free cisplatin was only 6.8 %. Therefore, t...Continue Reading

Citations

Feb 28, 2021·Colloids and Surfaces. B, Biointerfaces·Qianqian HanYanqing Wang
Jun 1, 2021·Journal of Colloid and Interface Science·Jiaxi XuRupei Tang

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