pH‐sensitive and charge‐reversal Daunorubicin‐conjugated polymeric micelles for enhanced cancer therapy

Abstract In this study, we prepared a novel pH‐sensitive drug delivery system based on Daunorubicin (DNR) using POEGMA‐ b ‐P(ABMA‐ co ‐AMA) (denoted as POPAA) as drug carrier which was prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization. A charge‐reversal prodrug (DA‐POPAA@imine‐DNR) was obtained after modified with 2,3‐dimethylmaleic anhydride (DA) by copper‐catalyzed alkyne‐azide “click chemistry.” The prodrug could self‐assemble into micelles (denoted as M(DNR)) with a mean particle size of about 132 nm. In vitro DNR release performances showed that there was a release of 13% at pH 7.4 while 73% at pH 5.0. Moreover, the zeta potential of M(DNR) could reserve from negative (−4.37 mV) to positive (+5.21 mV) as pH decreased from 7.4 to 6.5. The in vitro cytotoxicity assays showed that M(DNR) exhibited an efficient cell‐killing performance against HeLa cells. The above results confirmed the great potential of the DNR‐conjugated polymeric micelles for enhanced cancer therapy.