One-pot synthesis of glutathione-responsive amphiphilic drug self-delivery micelles of doxorubicin-disulfide-methoxy polyethylene glycol for tumor therapy.

We present a novel glutathione-responsive amphiphilic drug self-delivery (DSD) micelle with one-pot synthesis to synergistically address the problems of controlled drug release, degradability, drug tracing and in vivo accumulated toxicity. The anticancer drug doxorubicin (DOX), disulfide-based diacrylate (DSDA) and amino-polyethylene glycol monomethyl ether were linked by Michael addition in one-pot synthesis. The accumulative release rate of DOX analogues with drug activity from the micelles was 67.9% under pH 7.4 and GSH = 1 mg mL conditions after 72 h. The cell uptake experiment showed that the micelles of DOX-DSDA-PEG were indeed taken up by A549 cells and distributed to cell nuclei. The in vitro cell viability of A549 cells was evaluated by CCK-8 and Muse Annexin V & Dead Cell Kit. The results illustrated that the completely biodegradable micelles with glutathione-responsive bonds in the backbone are an effective drug self-delivery system for tumor therapy in the future.