Aggregation-Induced Photosensitization of Long-Chain-Substituted Osmium Complexes for Lysosomes Targeting Photodynamic Therapy

作者：Ziyu Zhou, Shuo Li, Xiuqian Ding, Kun Zhang, Jie Zhou, Xin Zhou · 发表于：ACS Applied Bio Materials · 年份：2025 · DOI：10.1021/acsabm.5c00224 · 被引用次数：7 · 研究领域：Nanoplatforms for cancer theranostics、Porphyrin and Phthalocyanine Chemistry、Photodynamic Therapy Research Studies

Photodynamic therapy (PDT) has been demonstrated to be an effective tool for cancer treatment. Seeking organelle-targeting photosensitizers (PSs) with robust reactive oxygen species (ROS) production is extremely in demand. Herein, we propose an aggregation-induced photosensitization strategy for effective PDT with osmium complexes. We designed and synthesized three osmium complexes ( Os-Me, Os-tBu, and Os-Nonly ) with ligands of different alkyl chains. In phosphate-buffered saline solution, the complex Os-Nonly formed a spherical aggregate with diameters of around 220 nm. The results from ROS assays indicate that Os-Nonly showed the highest efficiency in generating superoxide anions and singlet oxygen, demonstrating its role as a type I/II photosensitizer. Additionally, Os-Nonly specifically targeted lysosomes in 4T1 and MCF-7 cells, producing ROS in a sustained and efficient manner with high phototoxicity (IC 50 = 6.999 μM in MCF-7 cells), thereby inducing cancer cell death. In 4T1-tumor-bearing mice models, Os-Nonly effectively inhibited tumor growth with a minimal impact on normal organs.