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

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.