PD-L1 Aptamer-Functionalized Metal-Organic Framework Nanoparticles for Robust Photo-Immunotherapy Against Cancer with Enhanced Safety.

Immune checkpoint blockade has become a paradigm-shifting treatment modality to combat cancer, while conventional administration of immune checkpoint inhibitors, such as anti-PD-L1 antibody (α-PD-L1), often shows unsatisfactory immune responses and lead to severe immune-related adverse effects (irAEs). Herein, we develop a PD-L1 aptamer (aptPD-L1) based spherical nucleic acids (SNAs), which consists of an oxaliplatin (OXA) encapsulated metal-organic framework nanoparticle core and a dense shell of aptPD-L1 (denoted as M@O-A). Upon light irradiation, such nanosystem enables concurrent photodynamic therapy (PDT), chemotherapy and enhanced immunotherapy on one shot to inhibit both primary colorectal tumors and untreated distant tumors in mice. Notably, M@O-A shows scarcely any systemic immunotoxicity in a clinical irAEs-mimic transgenic mouse model. Collectively, this study presents a novel strategy for priming robust photo-immunotherapy against cancer with enhanced safety.