Chen Tianbao, Xu Shuting, Huang Wei, Yan Deyue
School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
Frontiers Science Center of Transformative Chemistry, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
Biomater Sci. 2022 Jul 12;10(14):3901-3910. doi: 10.1039/d2bm00739h.
Hypoxia-induced multi-drug resistance (MDR) often develops in the chemotherapy process of most anticancer drugs (, doxorubicin, DOX) and results in treatment failure in the clinic. Herein, a PEG-Pt(IV) prodrug was co-self-assembled with DOX into nanodrugs (PEG-Pt(IV)@DOX NPs). They can accumulate in tumor sites due to their longer blood retention half-life. Under light irradiation, the PEG-Pt(IV) prodrug can self-generate oxygen (O) to reduce the hypoxic zone in tumor tissue effectively and simultaneously release active -Pt(II) and DOX. The increasing O concentration in the tumor tissue can raise the level of reactive oxygen species (ROS) produced from DOX and significantly enhance the cytotoxicity of DOX to inhibit tumor proliferation by combining with active -Pt(II). Finally, the hypoxia-induced MDR of DOX can be alleviated. More importantly, the enhanced cytotoxicity of DOX is limited to the tumor site, which can effectively reduce its side effects on normal tissues. In summary, this would be a promising platform for the combination chemotherapy of hypoxia solid tumors in the clinic.
缺氧诱导的多药耐药（MDR）在大多数抗癌药物（如阿霉素，DOX）的化疗过程中经常出现，并导致临床治疗失败。在此，一种聚乙二醇-铂（IV）前药与DOX共同自组装成纳米药物（聚乙二醇-铂（IV）@DOX纳米粒子）。由于它们具有更长的血液滞留半衰期，它们可以在肿瘤部位积聚。在光照射下，聚乙二醇-铂（IV）前药可以自产生氧气（O）以有效减少肿瘤组织中的缺氧区域，同时释放活性铂（II）和DOX。肿瘤组织中不断增加的O浓度可以提高由DOX产生的活性氧（ROS）水平，并通过与活性铂（II）结合显著增强DOX的细胞毒性以抑制肿瘤增殖。最后，DOX的缺氧诱导MDR可以得到缓解。更重要的是，DOX增强的细胞毒性仅限于肿瘤部位，这可以有效降低其对正常组织的副作用。总之，这将是临床上用于缺氧实体瘤联合化疗的一个有前景的平台。
