Cancer photodynamic therapy (PDT) represents an attractive local treatment in combination with immunotherapy. Successful cancer PDT relies on image guidance to ensure the treatment accuracy. However, existing nanotechnology for co-delivery of photosensitizers and image contrast agents slows the clearance of PDT agents from the body and causes a disparity between the release profiles of the imaging and PDT agents. We have found that the photosensitizer Chlorin e6 (Ce6) is inherently bound to immunoglobulin G (IgG) in a nanomolarity range of affinity. Ce6 and IgG self-assemble to form the nanocomplexes termed Chloringlobulin (Chlorin e6 + immunoglobulin G). Chloringlobulin enhances the Ce6 concentration in the tumor without changing its elimination half-life in blood. Utilizing the immune checkpoint inhibitor antiprogrammed death ligand 1 (PD-L1) (αPD-L1) to prepare αPD-L1 Chloringlobulin, we have demonstrated a combination of Ce6-based red-light fluorescence image-guided surgery, stereotactic PDT, and PD-L1 blockade therapy of mice bearing orthotopic glioma. In mice bearing an orthotopic colon cancer model, we have prepared another Chloringlobulin that allows intraoperative fluorescence image-guided PDT in combination with PD-L1 and cytotoxic T lymphocyte antigen 4 (CTLA-4) dual checkpoint blockade therapy. The Chloringlobulin technology shows great potential for clinical translation of combinatorial intraoperative fluorescence image-guided PDT and checkpoint blockade therapy.
Keywords: Chlorin e6; cytotoxic T-lymphocyte-associated antigen 4; fluorescence image-guided surgery; immunoglobulin G; photodynamic therapy; programmed death ligand 1.