Type I photodynamic therapy with a self-degradable conjugated polyelectrolyte in combination with CpG adjuvant for cancer immunotherapy

•Self-degradable conjugated polyelectrolyte for controlled release of immune adjuvant (CpG) and excellent biocompatibility.•Aggregation-induced emission for enhanced photodynamic effect.•Type I photodynamic therapy for efficiency anti-hypoxia effect.•Combination of photodynamic therapy and immunotherapy for inhibiting metastatic cancer. In Photodynamic therapy (PDT), reactive oxygen species (ROS) generated by photosensitizers (PSs) can cause endoplasmic reticulum oxidative stress response to induce immunogenic cell death (ICD). However, most PDT-induced ICD cannot generate enough antitumor immune responses to inhibit metastatic cancer. Here, we developed a self-degradable conjugated polyelectrolyte (CP+) to load the immune adjuvant (CpG) for the combination of PDT and immunotherapy. Interestingly, the final nanoparticles (CP+-CpG NPs) can effectively generate superoxide radical (O2−•) through type-I process under light irradiation, which is ideal for hypoxic tumor treatment. Meanwhile, CP+-CpG NPs can be degraded by the self-generated O2−• in return to release the CpG. The release of CpG can further promote PDT-induced ICD, activating immune responses and inducing systemic antitumor immunity. Taken together, a novel strategy has been developed to enhance PDT therapeutic effects and induce immunotherapy, which is greatly promising for cancer treatment in the future.