Boosting anti-tumor immunity with boron-based nanosheets via photodynamic-elicited pyroptosis and adjuvant delivery.

Abstract

Photodynamic therapy (PDT) has emerged as a promising non-invasive therapeutic modality for tumor treatment. Moreover, PDT has the potential to induce immunogenic cell death (ICD), and its combination with immunotherapeutic strategies has become a promising approach for tumor therapy. In this study, we designed a multifunctional nanoplatform, IR@BP-L, which integrates PDT-induced pyroptosis with loxoribine as an immune agonist. On one hand, the effective accumulation of IR@BP-L at the tumor site enables PDT treatment via near-infrared light irradiation, generating a large amount of reactive oxygen species (ROS) to induce pyroptosis and promote local immunity. On the other hand, loxoribine is responsively released under near-infrared light irradiation and within the weakly acidic tumor microenvironment, thereby enhancing immune activation at the tumor site. As a TLR7 agonist, loxoribine effectively stimulates dendritic cell maturation, thereby potentiating T cell-dependent antitumor immunity. This co-delivery system amplifies immune activation by combining PDT-induced pyroptosis with immune agonist, leading to more effective antitumor outcomes. The nanoplatform demonstrated excellent immune activation effects and the ability to reverse the immunosuppressive tumor microenvironment after intravenous administration. Our strategy offered valuable insights for the development of a synergistic strategy for cancer immunotherapy.