Construction of Long-Wavelength Emissive Organic Nanosonosensitizer Targeting Mitochondria for Precise and Efficient In Vivo Sonotherapy

作者：Zhang, Xiangqian; Li, Chonglu; Zhang, Yi; Guan, Xiaofang; Mei, Longcan; Feng, Huili; Li, Jie; Tu, Le; Feng, Guoqiang; Deng, Ganzhen; Sun, Yao^*

来源：Advanced Functional Materials, 2022, 32(40): 2207259.

DOI：10.1002/adfm.202207259

• cancer therapy
• mitochondria-targeted
• NIR-II region
• organic nanosonosensitizer
• sonodynamic therapy

As a modern biomedical therapeutic modality, sonodynamic therapy (SDT) presents unique advantages, including superior tissue penetration capability, temporal-spatial controllability, and negligible side effects. However, the bottlenecks of most organic sonosensitizers are their short emission wavelengths, strong phototoxicity, and unsatisfactory SDT effect, which undermines the precise fluorescence imaging-guided SDT in vivo. Here, a long-wavelength emissive and mitochondria-targeted organic nanosonosensitizer, named CCNU980 nanoparticles (NPs), is rationally designed, which possesses deep-tissue optical penetration (up to 6 mm), depth-activated ROS production (up to 8 cm), high photostability, and low phototoxicity. In vitro studies verify CCNU980 NPs selectively enriches in cancer cells with the ability to target the mitochondria and induce mitochondria-mediated apoptosis using abundant O-1(2) under US irradiation. Notably, CCNU980 NPs enables precise in vivo NIR-II fluorescence imaging-guided SDT, accompanied by the suppression of the bilateral 4T1 tumor growth with minimal side effects. The current work can inspire a general strategy for the design of organic nanosonosensitizers with long-wavelength emission and new thoughts for precision medicine.

• 单位
  华中农业大学; 南京大学; y