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Intracellular Delivery of Colloidally Stable Core-Cross-Linked Triblock Copolymer Micelles with Glutathione-Responsive Enhanced Drug Release for Cancer Therapy.

Authors: Biswas DAn SYLi YWang XOh JK


Affiliations

1 Department of Chemistry and Biochemistry, Concordia University , Montreal, Quebec Canada H4B 1R6.
2 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College , No. 151, Malianwa North Road, Haidian District, Beijing 100193, China.

Description

Intracellular Delivery of Colloidally Stable Core-Cross-Linked Triblock Copolymer Micelles with Glutathione-Responsive Enhanced Drug Release for Cancer Therapy.

Mol Pharm. 2017 08 07;14(8):2518-2528

Authors: Biswas D, An SY, Li Y, Wang X, Oh JK

Abstract

Design and development of amphiphilic block copolymer-based nanocarriers exhibiting enhanced colloidal stability upon dilution in the blood and cellular glutathione-responsive rapid drug release is highly desired for tumor-targeting chemotherapy. Herein, we report a novel ABA-type triblock copolymer consisting of a hydrophilic central poly(ethylene glycol) block and two terminal hydrophobic blocks of a polymethacrylate having pendant disulfides (PHMssEt), thus PHMssEt-b-PEG-b-PHMssEt (ssTP). Aqueous self-assembly and the following disulfide-exchange reaction of the resulting ssTP allow for formation of core-cross-linked micelles (CCMs) through the formation of new disulfide linkages, retaining enhanced colloidal stability in physiological conditions and in the presence of proteins. Further, they exhibit reduction-responsive enhanced release of encapsulated drugs in response to cellular concentrations of glutathione in cancer cells, confirmed by dynamic light scattering and spectroscopic analysis. Combined with these results, in vitro (cells) and in vivo (mouse model) biological results suggest that ssTP-based CCMs are effective candidates as intracellular nanocarriers targeting tumors for cancer therapy.

PMID: 28207270 [PubMed - indexed for MEDLINE]


Links

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28207270?dopt=Abstract