Open‐Shell Nanosensitizers for Glutathione Responsive Cancer Sonodynamic Therapy
Han Wang, Jinxiao Guo, Wilson Lin, Zi Fu, Xiuru Ji, Bo Yu, Min Lü, Wenguo Cui, Lianfu Deng, Jonathan W. Engle, Zhiyuan Wu, Weibo Cai, Dalong Ni
Abstract
Abstract Deleterious effects to normal tissues and short biological half‐life of sonosensitizers limit the applications of sonodynamic therapy (SDT). Herein, a new sonosensitizer (Cu(II)NS) is synthesized that consists of porphyrins, chelated Cu 2+ , and poly(ethylene glycol) (PEG) to overcome the challenges of SDT. As Cu 2+ contains 27 electrons, Cu(II)NS has an unpaired electron (open shell), resulting in a doublet ground state and little sonosensitivity. Overexpressed glutathione in the tumor can reduce Cu 2+ to generate Cu(I)NS, leading to a singlet ground state and recuperative sonosensitivity. Additionally, PEG endows Cu(II)NS with increased blood biological half‐life and enhanced tumor accumulation, further increasing the effect of SDT. Through regulating the valence state of Cu, cancer SDT with enhanced therapeutic index is achieved.