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.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Biswas D,An SY,Li Y,Wang X,Oh JKdoi
10.1021/acs.molpharmaceut.6b01146subject
Has Abstractpub_date
2017-08-07 00:00:00pages
2518-2528issue
8eissn
1543-8384issn
1543-8392journal_volume
14pub_type
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