ZnO Quantum Dots Modified by pH-Activated Charge-Reversal Polymer for Tumor Targeted Drug Delivery

In this paper, we reported a pH responsive nano drug delivery system (NDDS) based on ZnO quantum dots (QDs) for controlled release of drugs. Zwitterionic poly(carboxybetaine methacrylate) (PCBMA) and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) were introduced to modify ZnO QDs, which can help enhance water stability, increase blood circulation time, and promote endocytosis. After tuning of PCBMA/PDMAEMA ratios, the ZnO@P(CBMA-co-DMAEMA) nanoplatform shows a sensitive switch from strong protein adsorption resistance (with negatively charged surface) at physiological pH to strong adhesion to tumor cell membranes (with positively charged surface) at the slightly acidic extracellular pH of tumors. Anti-cancer drug, Doxorubicin (DOX), molecules were demonstrated to be successfully loaded to ZnO@P(CBMA-co-DMAEMA) with a relatively large drug loading content (24.6%). In addition, ZnO@P(CBMA-co-DMAEMA) loaded with DOX can achieve lysosomal acid degradation and release of DOX after endocytosis by tumor cells, resulting in synergistic treatment of cancer, which is attributed to a combination of the anticancer effect of Zn2+ and DOX.