Chondroitin sulfate-based prodrug nanoparticles enhance photodynamic immunotherapy via Golgi apparatus targeting

Photodynamic therapy (PDT) is an emerging therapeutic approach that can inhibit tumor growth by destroying local tumors and activating systemic antitumor immune responses. However, PDT can be ineffective because of photosensitizer aggregation, tumor-induced dendritic cells (DCS) dysfunction and PDT-mediated immunosuppression. Therefore, we designed chondroitin sulfate-based prodrug nanoparticles for the co-delivery of the photosensitizer chlorin e6 (Ce6) and retinoic acid (RA), which can reduce PDT-mediated immunosuppression by disrupting the Golgi apparatus and blocking the production of immunosuppressive cytokines. Moreover, CpG oligodeoxynucleotide was combined as immunoadjuvant to promote the maturation of DCs. As expected, the strategy of Golgi apparatus targeting immunotherapy combined PDT was confirmed to relieve PDT-induced immunosuppression, showed excellent PDT antitumor efficacy in B16F10-subcutaneous bearing mice model. Thus, our finding offers a promising approach for photodynamic immunotherapy of advanced cancers. STATEMENT OF SIGNIFICANCE: Golgi apparatus has been shown to be a potential target of immunosuppression for producing several immunosuppressive cytokines. In this work, a Golgi apparatus-targeted prodrug nanoparticle was developed to enhance the immune response in photodynamic immunotherapy. The nanoparticle can target and disrupt the Golgi apparatus in tumor cells, which reduced PDT-mediated immunosuppression by blocking the production of immunosuppressive cytokines. This work provides an effective strategy of PDT in combination with the Golgi apparatus-targeted nanovesicle for enhanced cancer therapy.