Engineering antigen as photosensitiser nanocarrier to facilitate ROS triggered immune cascade for photodynamic immunotherapy

Despite of the documented immunogenic cell death (ICD) and antigen cross-presentation (AC) in photodynamic therapy (PDT), the overall immune efficacy is rather limited. This study aims to expand the immune potential of PDT by spatially packaging antigen as photosensitiser nanocarrier to trigger efficient immune cascade for photodynamic immunotherapy. The package of ovalbumin antigen (OVA) into sub-100 nm nano-assembly is realized by driving intermolecular disulfide network between OVA molecules. OVA nanoparticles loading photosensitiser Ce6 (ON) are subsequently coated with B16-OVA cancer cell membrane, resulting in membrane cloaked ON (MON). Importantly, laser irradiation generated ROS significantly potentiates OVA antigen cross-presentation efficiency. Whilst, MON is endowed with homophilic targeting towards tumor due to cancer cell membrane coating. In treating B16-OVA tumor-bearing mice, MON effectively triggers the immune cascade, completely eliminates the tumor under laser irradiation and provokes a long-term antitumor immune memory effect. Conversely, a marginal effect is found if substituting OVA for bovine serum protein (BSA) in nanoparticle design or using MON to treat non-OVA expressing tumor. The antigen nanocarrier design promises to complement conventional PDT by boosting immune cascade, thereby leading to unique photodynamic immunotherapy.