STING-Activating nanoplatforms for image-guided sonodynamic cancer therapy.

Tumor precision treatment still faces the challenge of being unable to achieve real-time monitoring. The rapid advancements in nanomedicine within the biomedical sector have highlighted the potential of integrated nano-platforms for tumor diagnosis and treatment. Herein, we create a multimodal diagnostic nanodrug, ⁹⁹mTc-NPAIE-MSA, which combines sonosensitizers, STING agonists, and radionuclides for immuno-sonodynamic therapy targeting breast cancer. This platform utilizes polymers with aggregation-induced luminescence properties that, when activated by US, generate cytotoxic reactive oxygen species, causing DNA and mitochondrial damage, activating the cGAS-STING pathway, and releasing the STING agonist MSA-2 to enhance the immune response. Additionally, ⁹⁹mTc incorporation facilitates SPECT/CT and near-infrared fluorescence imaging, thereby improving tumor targeting and therapeutic monitoring precision. Both in vitro and in vivo studies confirm the significant anti-tumor effects and immunomodulation achieved by this nano-platform under US, presenting a novel strategy for precise tumor diagnosis and treatment.