Precise ratiometric loading of PTX and DOX based on redox-sensitive mixed micelles for cancer therapy

A new redox-sensitive drug delivery system with a precise ratiometric loading and different anticancer mechanisms (PTX and DOX) is constructed for cancer therapy. [Display omitted] •The ratio of PTX and DOX in the mixed micelles is precisely fixed.•The mixed micelles realize the redox-triggered release of PTX and DOX.•The mixed micelles can enhance anticancer effect and reduce system toxicity. PTX and DOX have different anticancer mechanisms. The combination of the two anticancer drugs could synergically enhance their anticancer effect, but simultaneously accompanied by severe side effects. In the present study, we constructed a mixed micelle system based on redox-sensitive mPEG-SS-PTX and mPEG-SS-DOX conjugate. The drug delivery system has a fixed and high drug loading content of 24.2% (PTX∼14.8% and DOX∼9.4%) with a precise ratio of PTX and DOX to realize the synchronized and controlled release. The mixed micelle has an average size of 93.3nm with a narrow distribution, suitable for passive targeting to tumor tissues by the EPR effect. In vitro release profile and in vitro anticancer results show the mixed micelles have obvious redox-sensitive release properties in reducing environment and have a significant cytotoxicity to A549 and B16 cells. Importantly, in vivo study shows the mixed micelles have no obvious side effect on mice compared to free PTX/DOX samples during the treatment. Therefore, the constructed redox-sensitive mixed micelle is a promising drug delivery system for cancer therapy.