Endoplasmic Reticulum Targeting Nanoparticle for Efficient Anti-Tumor Immunotherapy

Despite significant clinical breakthroughs in anti-tumor immunotherapy, its therapy efficiency remains hindered by insufficient "cold" tumor immune responses. The ample reactive oxygen species in photodynamic therapy (PDT) can trigger the immunogenic cell death (ICD) pathway for arousing the tumor system and realizing tumor immunotherapy. But the inherent hypoxic tumor microenvironment (TME) limits PDT efficacy. To simultaneously reverse the hypoxic TME and promote the ICD pathway, the multi-in-one nanostructure (FAIC) is designed, in which the catalase (CAT) and photosensitizer (I-Cy5) are encapsulated in a folate receptor-targeting liposome. Due to the endoplasmic reticulum (ER)-targeting ability of I-Cy5, H2O2 decomposition catalytic ability of CAT, and the tumor cell-targeting ability of folate receptor-targeting liposome, severe ER stress is triggered by the nano FAIC for arousing the ICD pathway. As a result, the infiltration of cytotoxic T lymphocytes is promoted, and the anti-tumor immune response is boosted. The design of nano FAIC and the corresponding mechanism provide a potential way to realize efficient tumor immunotherapy.