Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, China.
Department of Chemistry, University of Utah, Salt Lake City, UT 84112.
Proc Natl Acad Sci U S A. 2022 May 17;119(20):e2202255119. doi: 10.1073/pnas.2202255119. Epub 2022 May 11.
Combination chemotherapy, which involves the simultaneous use of multiple anticancer drugs in adequate combinations to disrupt multiple mechanisms associated with tumor growth, has shown advantages in enhanced therapeutic efficacy and lower systemic toxicity relative to monotherapy. Herein, we employed coordination-driven self-assembly to construct discrete Pt(II) metallacycles as monodisperse, modular platforms for combining camptothecin and combretastatin A4, two chemotherapy agents with a disparate mechanism of action, in precise arrangements for combination chemotherapy. Formulation of the drug-loaded metallacycles with folic acid–functionalized amphiphilic diblock copolymers furnished nanoparticles with good solubility and stability in physiological conditions. Folic acids on the surface of the nanoparticles promote their internalization into cancer cells. The intracellular reductive environment of cancer cells induces the release of the drug molecules at an exact 1:1 ratio, leading to a synergistic anticancer efficacy. In vivo studies on tumor-bearing mice demonstrated the favorable therapeutic outcome and minimal side effects of the combination chemotherapy approach based on a self-assembled metallacycle.
联合化疗，即同时使用多种抗癌药物进行适当组合，以破坏与肿瘤生长相关的多种机制，相对于单药治疗显示出了增强疗效和降低全身毒性的优势。在这里，我们采用配位驱动的自组装方法构建离散的 Pt(II) 金属环作为单分散、模块化的平台，将两种作用机制不同的化疗药物喜树碱和康普瑞汀 A4 以精确的组合化疗方式组合在一起。用叶酸功能化的两亲性嵌段共聚物将负载药物的金属环制剂化，得到了在生理条件下具有良好溶解度和稳定性的纳米粒子。纳米粒子表面的叶酸促进了它们进入癌细胞的内化。癌细胞内的还原环境以精确的 1:1 比例诱导药物分子的释放，从而产生协同的抗癌疗效。在荷瘤小鼠的体内研究中，基于自组装金属环的组合化疗方法表现出了良好的治疗效果和最小的副作用。
