A pH-Responsive Charge-Convertible Drug Delivery Nanocarrier for Precise Starvation and Chemo Synergistic Oncotherapy

Graphical A pH-responsive charge-convertible MTGZ@PPD drug delivery nanocarrier has been designed and fabricated for precise starvation and chemo synergistic oncotherapy. A pH-responsive charge-convertible drug delivery nanocarrier (MSN-TPZ-GOx@ZnO@PAH-PEG-DMMA, abbreviated as MTGZ@PPD) was prepared, which could specifically release hypoxia-activated chemotherapeutic Tirapazamine (TPZ) and glucose oxidase (GOx) in the tumor site for precise starvation and chemo synergistic oncotherapy. Acid-responsive Schiff base structure modified mesoporous silica nanoparticles (MSN) co-load with GOx and TPZ, then link with ZnO quantum dots (QDs). PAH-PEG-DMMA (PPD) polymer makes MTGZ@PPD with biocompatibility and charge-convertible feature. MTGZ@PPD is negatively charged at physiological pH, and the charge reversal of PPD and acidolysis of the Schiff base structure under the acidic tumor microenvironment (TME) induce a positively charged surface, which could potentiate the cell internalization. ZnO QDs could decompose at acidic TME, achieving controllable drug release. GOx could starve the tumor cells and enhance hypoxia level, thus initiates the activation of TPZ to realize synergistic starvation therapy and chemotherapy. This intelligent MTGZ@PPD has shown great potential for starvation and chemo synergistic oncotherapy.