Carrier-adjuvanted immunostimulator to boost photodynamic immunotherapy by downregulating PD-L1 and impairing ATP hydrolysis

Abstract

Immune evasion behavior and immunosuppressive characteristics of tumor extensively impede the immune initiation effect of therapy triggered immunogenic cell death (ICD). In this work, a carrier-adjuvanted immunostimulator (designated as CoCeC) is developed to boost photodynamic immunotherapy by downregulating programmed death ligand 1 (PD-L1) and impairing adenosine triphosphate (ATP) hydrolysis. Among these, the crosslinked chitosan oligosaccharide is applied as the drug carrier for delivery of Ce6 and Ceritinib, which also serves as an immune adjuvant to downregulate PD-L1. Meanwhile, the robust photodynamic therapy (PDT) of CoCeC exhibits lethal toxicity against tumor cells to induce ICD and release damage-associated molecular patterns (DAMPs), which can also impair ATP hydrolysis by blocking CD39. In vitro and in vivo results demonstrate the robust therapeutic efficacy of CoCeC to suppress primary tumor growth and activate a superior immune elimination against lung metastasis by amplifying the immune initiation of ICD with the assistance of immune adjuvants. This work provides a self-adjuvanted strategy to enhance the immune response of therapy induced ICD, which is promising to activate systemic antitumor immunity in consideration of the complicated immunosuppressive factors.