Doxorubicin delivered by a redox-responsive dasatinib-containing polymeric prodrug carrier for combination therapy.

ABSTRACT: Two novel prodrug polymers POEG-b-PSSDas (redox-sensitive) and POEG-b-PCCDas (redox-insensitive), which consist of poly(oligo(ethylene glycol) methacrylate) (POEG) hydrophilic blocks and dasatinib (DAS, an oncogenic tyrosine kinases inhibitor) conjugated hydrophobic blocks, were designed as dual-functional carriers for codelivery with doxorubicin (DOX). Both carriers retained antitumor activity of DAS and could form mixed micelles with DOX. Compared to POEG-b-PCCDas micelles, incorporation of disulfide linkage into POEG-b-PSSDas micelles facilitated efficient cleavage of DAS from prodrug micelles in tumor cells/tissues, leading to a higher level of anti-tumor activity in vitro and in vivo. In addition, DOX-loaded POEG-b-PSSDas micelles exhibited triggered DOX release under a redox environm

SUBMITTER: Sun J 

PROVIDER: S-EPMC5525542 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature