可逆的金属配位开关通过双重死亡和免疫协同作用实现可激活的声动力疗法
Zihui Liu1, Fei Li1, Jialong Sun1
1College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, China.
Abstract:
Sonodynamic therapy (SDT) holds great potential for disease treatment, yet its efficacy is limited by constitutive reactive oxygen species (ROS) generation and poor selectivity. Herein, we report a generalizable strategy using reversible metal-ion coordination to regulate the sonodynamic activity of semiconducting polymers (SPs). A diketopyrrolopyrrole (DPP)-based polymer (SPC) serves as the coordination scaffold, where binding with transition metal ions (Cu2+, Co2+, Zn2+, Fe3+) redistributes electron density and increases the singlet-triplet energy gap (ΔEST), thereby effectively suppressing ROS generation. Among them, Cu2+ is selected as a model ion due to its reductive responsiveness to glutathione (GSH) in the tumor microenvironment (TME). This enables SPCu to remain inactive during systemic circulation and become selectively reactivated within the TME. Released copper further induces mitochondrial dysfunction and cuproptosis, synergizing with ultrasound-triggered ROS-driven PANoptosis. Together, this dual-death mechanism elicits robust tumor ablation, immunogenic cell death, and immune cell activation, leading to systemic antitumor immunity. Collectively, this study presents a reversible, metal coordination-based platform for constructing activatable organic sonosensitizers, offering precise SDT with immuno-therapeutic synergy.
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