Mitochondria-Targeted Degradable Nanocomposite Combined with Laser and Ultrasound for Synergistic Tumor Therapies.

Although the development of safe and efficient cancer therapeutic agents is essential, this process remains challenging. In this study, a mitochondria-targeted degradable nanoplatform (PDA-MnO₂-IR780) for synergistic photothermal, photodynamic, and sonodynamic tumor treatment was investigated. PDA-MnO₂-IR780 exhibits superior photothermal properties owing to the integration of polydopamine, MnO₂, and IR780. IR780, a photosensitizer and sonosensitizer, was used for photodynamic therapy and sonodynamic therapy. When PDA-MnO₂-IR780 was delivered to the tumor site, MnO₂ was decomposed by hydrogen peroxide, producing Mn and oxygen. Meanwhile, alleviating tumor hypoxia promoted the production of reactive oxygen species during photodynamic therapy and sonodynamic therapy. Moreover, large amounts of reactive oxygen species could reduce the expression of heat shock proteins and increase the heat sensitivity of tumor cells, thereby improving the photothermal treatment effect. In turn, hyperthermia caused by photothermal therapy accelerated the production of reactive oxygen species in photodynamic therapy. IR780 selectively accumulation in mitochondria also promoted tumor apoptosis. In this system, the mutual promotion of photothermal therapy and photodynamic therapy/sonodynamic therapy had an enhanced therapeutic effect. Moreover, the responsive degradable characteristic of PDA-MnO₂-IR780 in the tumor microenvironment ensured excellent biological safety. These results reveal a great potential of PDA-MnO₂-IR780 for safe and highly-efficiency synergistic therapy for cancer.