| Summary: | Sonodynamic therapy (SDT), as a novel cancer therapy strategy, might be a promising approach due to the depth-penetration property in tissue. Sonosensitizers are the key element for efficient SDT. However, the development of sonosensitizers with strong sonosensitization efficacy is still a significant challenge. Herein, an urchin-shaped copper-based metalloporphyrin liposome nanosystem (FA–L–CuPP) is constructed and identified as an excellent sonosensitizer. Under ultrasound (US) irradiation, FA–L–CuPP can be highly excited to generate several reactive oxygen species (ROS), such as singlet oxygen (<sup>1</sup>O<sub>2</sub>) and free radicals (⋅OH). The molecular orbital distribution calculations reveal that a strong intramolecular charge transfer might occur in the CuPP complex under US irradiation, which could afford enough energy to the surrounding O<sub>2</sub> and H<sub>2</sub>O to concert <sup>1</sup>O<sub>2</sub>, O<sub>2</sub><sup>−</sup> and ⋅OH. Working as “ammunitions”, the largely produced ROS can kill 4T1 tumor cells, effectively inhibiting tumor growth. This work provides an urchin-shaped nanosonosensitizer based on a copper complex, which might provide an idea to design a novel sonosensitizer for noninvasive and precise SDT antitumor applications.
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