Spatiotemporally Controlled Tumor Photodynamic/Immunotherapy Therapy Based on Upconversion Hybrid Nanosystem

Abstract Immunotherapy holds great promise for cancer treatment, but its clinical application is hindered by the immunosuppressive tumor microenvironment (TME) and the systematic toxicity. Herein, a spatiotemporally controllable smart nanodevice based on upconversion nanoparticles (UCNPs) that can be activated by dual near ‐ infrared (NIR) light for tumor immunotherapy, namely PURH, is developed. PURH is constructed by a five‐layer UCNPs surface coated with mesoporous silica, which encapsulates the photosensitizer rose bengal (RB) within the mesoporous channels. Additionally, CpG oligonucleotides (CpG ODN) is linked to the surface, followed by the surface functionalization of hyaluronic acid (HA) to achieve tumor targeting. PURH allows for dual NIR light activation, where 980 nm NIR light irradiation activates photodynamic therapy (PDT), inducing apoptosis and immunogenic cell death (ICD), while 808 nm NIR light irradiation triggers the release of CpG for tumor immunotherapy. The study offers a powerful tool and strategy for spatiotemporal controlled tumor immunotherapy.