A Cyclic Photosensitizer Nanoplatform for Effective Pyroptosis and Enhanced Photoimmunotherapy

Cyclic molecules exhibit distinct advantages in drug discovery and delivery. Herein, we synthesized a cyclic BODIPY photosensitizer (BR) and constructed a versatile platform for inducing pyroptosis and enhancing tumor photoimmunotherapy. Benefiting from the cyclic structure, BR could assemble into nanoparticles (BRNs) with robust long-term colloidal stability. The single-crystal X-ray diffraction result indicates that the intermolecular forces of BR are mainly π-π stacking interactions and H-bonds. Furthermore, the dimers of indoleamine 2,3-dioxygenase inhibitor were loaded to form BRGNs for alleviating immunosuppression tumor microenvironment. BRGNs generate reactive oxygen species and disrupt intracellular redox homeostasis upon irradiation, leading to mitochondrial damage and innate immunogenic pyroptosis. Subsequently, intracellularly abundant cytokines and contents are released to elicit robust immune responses for inhibiting the tumor growth. In brief, this work brings an approach to build cyclic carriers integrating phototherapy and immunotherapy.