title: Intracellular Delivery of Colloidally Stable Core-Cross-Linked Triblock Copolymer Micelles with Glutathione-Responsive Enhanced Drug Release for Cancer Therapy.
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.
authors.affiliation: Department of Chemistry and Biochemistry, Concordia University , Montreal, Quebec Canada H4B 1R6.
authors.forename: Depannita
authors.initials: D
authors.lastname: Biswas
authors.affiliation: Department of Chemistry and Biochemistry, Concordia University , Montreal, Quebec Canada H4B 1R6.
authors.forename: So Young
authors.initials: SY
authors.lastname: An
authors.affiliation: 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.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Xiangtao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, Concordia University , Montreal, Quebec Canada H4B 1R6.
authors.forename: Jung Kwon
authors.identifier: 0000-0002-4220-308X
authors.initials: JK
authors.lastname: Oh
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D008823:Micelles; D011108:Polymers / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D005978:Glutathione
keywords: cross-linked micelles; drug delivery; enhanced release; glutathione-responsive degradation; triblock copolymer