Zhou Yifei, Gao Xuan, Lu Yu, Zhang Ruohao, Lv Kehong, Gong Jitong, Feng Jing, Zhang Hongjie
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, P. R. China.
Chempluschem. 2023 Feb;88(2):e202200394. doi: 10.1002/cplu.202200394.
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.
制备了一种pH响应性电荷可转换药物递送纳米载体（MSN-TPZ-GOx@ZnO@PAH-PEG-DMMA，简称为MTGZ@PPD），其可在肿瘤部位特异性释放缺氧激活的化疗药物替拉帕米（TPZ）和葡萄糖氧化酶（GOx），用于精确饥饿和化疗协同肿瘤治疗。酸响应性席夫碱结构修饰的介孔二氧化硅纳米颗粒（MSN）与GOx和TPZ共同负载，然后与ZnO量子点（QDs）连接。PAH-PEG-DMMA（PPD）聚合物使MTGZ@PPD具有生物相容性和电荷可转换特性。MTGZ@PPD在生理pH下带负电荷，在酸性肿瘤微环境（TME）下PPD的电荷反转和席夫碱结构的酸解诱导表面带正电荷，这可增强细胞内化。ZnO量子点可在酸性TME中分解，实现可控药物释放。GOx可使肿瘤细胞饥饿并提高缺氧水平，从而启动TPZ的激活以实现协同饥饿治疗和化疗。这种智能的MTGZ@PPD在饥饿和化疗协同肿瘤治疗方面显示出巨大潜力。
