A pH-Responsive Charge-Convertible Drug Delivery Nanocarrier for Precise Starvation and Chemo Synergistic Oncotherapy.
Yifei ZhouXuan GaoYu LuRuohao ZhangKehong LvJitong GongJing FengHong-Jie ZhangPublished in: ChemPlusChem (2023)
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.
Keyphrases
- drug delivery
- cancer therapy
- drug release
- quantum dots
- room temperature
- machine learning
- sensitive detection
- endothelial cells
- deep learning
- squamous cell carcinoma
- single cell
- cell therapy
- stem cells
- metabolic syndrome
- visible light
- polycyclic aromatic hydrocarbons
- adipose tissue
- bone marrow
- mesenchymal stem cells
- energy transfer
- insulin resistance
- replacement therapy
- tissue engineering
- rectal cancer
- neural network