Mixed polycarbonate prodrug nanoparticles with reduction/pH dual-responsive and charge conversional properties

To build a multifunctional and biodegradable drug delivery system, positively and negatively charged functional polycarbonates (PCs) were synthesized and then assembled into nanoparticles (NPs) in pH 7.4 PBS via electrostatic and hydrophobic interaction. Hydrazone linked doxorubicin (DOX) and disulfide functional groups were conjugated to the propargyl-functional PC to achieve the positive PC, PC(Arss-N(CH3)2-DOX). In pH 7.4 PBS, the positive PCs could form charged NPs with reduction/pH dual sensitive behaviors. The negative PCs, poly(ethylene glycol)-block-1,2-dicarboxylic-cyclohexene anhydride modified amino polycarbonate (PEG-PCDCA) and PCDCA, were used to modulate the size/size distribution of the prodrug NPs and strengthen the blood circulation ability of the NPs. The surface nature of NPs could change from negative in physical pH to positive at tumor extracellular pH (pHe). In vitro study showed that the NPs could exhibit effective cellular uptake, intracellular drug release, and obvious cytotoxicity against Hela tumor cells. All these indicated that the NPs would be a potential for the anti-tumor drug delivery system.