Harnessing Ag₂S quantum dots with immune adjuvant for NIR-II fluorescence imaging-guided sonodynamic immunotherapy of colon cancer

The combination of sonodynamic therapy (SDT) with immunotherapy can not only overcome the limitations of immunotherapy such as poor responsiveness and high side effects but also improve the sensitivity of SDT. Here an integrated biomimetic nanoparticle was constructed for NIR-II fluorescence imaging-guided sonodynamic-immune combination therapy. Polymer micelles (Ag₂S@P) were synthesized by self-assembly of Ag₂S QDs and amphiphilic polymers Pluronic F-127, and the micelles were modified with the homologous adjuvant-embedded cancer cell membrane to generate a biomimetic nanocarriers Ag₂S@P@CM-A. The modified cancer cell membrane endowed nanoparticles homologous targeting ability. Under NIR-II fluorescence imaging-guided SDT, Ag₂S@P@M-A generates reactive oxygen species (ROS) induced immunogenic cell death (ICD) that is characterized by the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Meanwhile, the nanoparticles released toll-like receptor 4 agonist monophosphoryl lipid A (MPLA) in tumors, together with TAAs and DAMPs, to promote dendritic cell (DCs) maturation, cytotoxic T cells activation, and tumor infiltration, effectively inhibiting tumor growth. In combination with checkpoint blockade PD-L1, Ag₂S@P@M-A mediated sonodynamic-immunotherapy exhibited more potent anticancer efficacy. In conclusion, our study reported a promising therapeutic strategy for bridging the limitations of SDT and immunotherapy to enhance the efficacy of cancer therapy.