A light-controlled dextran nano-immunomodulator amplifies immunogenic cell death for cancer immunotherapy

Immunogenic cell death (ICD) is a programmed modality of regulated cell death that induces strong adaptive immune responses, which is severely related to the drug release kinetics of nanotherapeutics. Here, we report a light-controlled polysaccharide nano-immunomodulator (Dex-NB-CPT) with enhanced ICD induction for cancer immunotherapy. Dex-NB-CPT does not self-assemble into nanoparticles as a single-molecular micelle, and releases ICD inducer camptothecin (CPT) rapidly via a photocleavable linker under light illumination, avoiding the hindrance of nanoparticle disassembly and physical encapsulation to realize efficient drug release. Upon light illumination, the cell apoptosis of 4T1 and B16F10 cells was evaluated as compared with CPT and Dex-NB-CPT without light illumination. The ICD induction efficiency was also augmented after light illumination as validated by increased cellular calreticulin (CRT) and high mobility group protein B1 (HMGB1) levels, which further promoted macrophage M1 polarization and dendritic cell maturation. In a 4T1 tumor-bearing mice, Dex-NB-CPT with light illumination significantly inhibited 4T1 tumor growth by inducing robust ICD effect with much higher levels of CRT and HMGB1 to activate dendritic cells and cytotoxic T cells for enhanced cancer immunotherapy. Our work provides a robust strategy to potentiate cancer immunotherapy by augmenting ICD effect with a light-controlled polysaccharide nano-immunomodulator.