Photo-immunomodulatory multifunctional nanoliposomes targeting myeloid derived suppressor cells augment antitumor immunity for colon cancer.

The therapeutic effect of cancer immunotherapy is limited by immune resistance caused by the immunosuppressive tumor microenvironment (TME). While photodynamic therapy (PDT) can enhance tumor immunogenicity and initiate anti-tumor immunity, its practical benefits are limited. To address this, we developed a TME-responsive nanoliposome for the co-delivery of the photosensitizer chlorin e6 (Ce6) and the immunomodulatory agent AMD3100. Our results demonstrated that Ce6-mediated PDT effectively induced immunogenic cell death (ICD) in colon cancer cells, as evidenced by the robust surface exposure of calreticulin and the release of high mobility group box 1 (HMGB1). Simultaneously, AMD3100 significantly inhibited the infiltration of myeloid-derived suppressor cells (MDSCs) into the TME by blocking the CXCL12/CXCR4 axis. Combined treatment led to a remarkable 90.2 % inhibition of tumor growth in a murine CT26 colon carcinoma model. This profound antitumor effect was driven by a significant enhancement of dendritic cell (DC) maturation (31.1 %) and a 1.62-fold increase in tumor infiltration of CD8 + T cells, coupled with a 76.11 % reduction in MDSC accumulation. In conclusion, this multifunctional nanoliposome, which synergizes immunogenic PDT with targeted MDSC regulation, presents a highly effective strategy for colon cancer treatment and opens a new avenue for advanced photoimmunotherapy.