In the present investigation, the potential of a novel, self-assembled, biocompatible, and redox-sensitive copolymer system with disulfide bond was explored for doxorubicin (DOX) delivery through polymersome nanostructures of ∼120 nm. The polymer system was synthesized with less steps, providing a high yield of 86%. The developed polymersomes showed admirable biocompatibility with high dose tolerability in vitro and in vivo. The colloidal stability of DOX-loaded polymersomes depicted a stable and uniform particle size over a period of 72 h. The cellular internalization of polymersomes was assessed in HeLa and MDA-MB-231 cell lines, where enhanced cellular internalization was observed. The dose-dependent cytotoxicity was observed for DOX-loaded polymersomes by MTT cytotoxicity assay in the above cell lines. The tumor suppression studies were assessed in Ehrlich ascites tumor (EAT) carrying Swiss albino mice, where polymersomes exhibited a 7.16-fold reduction in tumor volume correlated with control and 5.39-fold higher tumor inhibition capacity compared to conventional chemotherapy (free DOX treatment). The developed polymersomes gave safer insights concerning DOX associated toxicities by histopathology and serum biochemistry analysis. Thus, results focus on the potential of redox responsive polymersomes for efficacious and improved DOX therapy with enhanced antitumor activity and insignificant cardiotoxicity which can be translated to clinical settings.
Keywords: doxorubicin; polycaprolactone; polyethylene glycol; polymersomes; redox sensitive.