Redox- and pH-Sensitive Polymeric Micelles Based on Poly(β-amino ester)-Grafted Disulfide Methylene Oxide Poly(ethylene glycol) for Anticancer Drug Delivery

In this report, a redox- and pH-sensitive poly(β-amino ester)-grafted disulfide methylene oxide poly(ethylene glycol) (PAE-g-DSMPEG) was synthesized, and it showed not only a sharp pH-dependent assembly-disassembly transition but also a quick shell shading in a high concentration of reducing agent by Michael addition polymerization. ¹H NMR, dynamic light scattering, and transition electron microscopy were combined to characterize the redox- and pH-responsiveness in various triggered conditions. The hydrophobic drug doxorubicin (DOX) was used as the model drug to investigate the encapsulation and delivery ability of polymeric micelles, in both in vitro and in vivo experiments. Notably, antitumor experiments in tumor-bearing mice showed that DOX-loaded polymeric micelles effectively enhanced the therapeutic efficacy in comparison to free-DOX. These results were further confirmed by histopathological examinations. Taken together, the results suggested that PAE-g-DSMPEG could be a potential hydrophobic drug delivery vehicle.