MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510006, P. R. China.
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Angew Chem Int Ed Engl. 2022 Jul 11;61(28):e202205429. doi: 10.1002/anie.202205429. Epub 2022 May 24.
The clinical application of photodynamic therapy is hindered by the high glutathione concentration, poor cancer-targeting properties, poor drug loading into delivery systems, and an inefficient activation of the cell death machinery in cancer cells. To overcome these limitations, herein, the formulation of a promising Ir complex into a biodegradable coordination polymer (IrS NPs) is presented. The nanoparticles were found to remain stable under physiological conditions but deplete glutathione and disintegrate into the monomeric metal complexes in the tumor microenvironment, causing an enhanced therapeutic effect. The nanoparticles were found to selectively accumulate in the mitochondria where these trigger cell death by hybrid apoptosis and ferroptosis pathways through the photoinduced production of singlet oxygen and superoxide anion radicals. This study presents the first example of a coordination polymer that can efficiently cause cancer cell death by apoptosis and ferroptosis upon irradiation, providing an innovative approach for cancer therapy.
光动力疗法的临床应用受到高谷胱甘肽浓度、缺乏癌症靶向特性、难以将药物载入递送系统以及癌细胞中细胞死亡机制的激活效率低下的限制。为了克服这些限制，本文将一种有前途的 Ir 配合物制成了一种可生物降解的配位聚合物（IrS NPs）。研究发现，这些纳米粒子在生理条件下保持稳定，但会耗尽谷胱甘肽并在肿瘤微环境中分解为单体金属配合物，从而增强治疗效果。这些纳米粒子被发现选择性地积聚在线粒体中，通过光诱导产生单线态氧和超氧阴离子自由基，通过混合细胞凋亡和铁死亡途径触发细胞死亡。本研究首次提出了一种配位聚合物的实例，它可以通过照射有效地通过细胞凋亡和铁死亡导致癌细胞死亡，为癌症治疗提供了一种创新方法。
