Yeast Nanoparticle‐powered Tumor Photodynamic‐Immunotherapy

Photodynamic therapy (PDT) uses a combination of light and a photosensitizing agent to destroy cancerous cells. However, the PDT alone often insufficient to elicit an effective anti-tumor response due to various factors including insufficient ROS generation and the weak induced immune response. Here, we report yeast nanoparticles (YNPs) loaded with aggregation-induced emission (AIE) photosensitizer QMC12 (YNP-QMC) for enhanced photodynamic-immunotherapy in animal models. YNPs have a strong immune adjuvant effect which could significantly activate various APCs and reverse the immunosuppressive microenvironment at tumor and tumor-draining lymph nodes (TDLNs) sites. More importantly, YNP-QMC can be attached with tumor cell antigens released from dying cells after PDT. This antigen attached nanoparticle can efficiently migrate to tumor-draining lymph nodes and activate an antigen-specific systemic antitumor immunity. In combination with anti-PD-L1, this strategy could promote the elimination of primary tumors and inhibit the growth of distant tumors. Thus, our AIE photosensitizer and adjuvant YNP-powered PDT strategy provides a simple way to enhance efficacy of PDT.