title: Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy.
abstract: Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT). Synergy between oxaliplatin and pyrolipid-induced PDT kills tumour cells and provokes an immune response, resulting in calreticulin exposure on the cell surface, antitumour vaccination and an abscopal effect. When combined with anti-PD-L1 therapy, NCP@pyrolipid mediates regression of both light-irradiated primary tumours and non-irradiated distant tumours by inducing a strong tumour-specific immune response.
authors.affiliation: Department of Chemistry, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Chunbai
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Chemistry, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Xiaopin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Chemistry, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA.|Department of Radiation and Cellular Oncology and The Ludwig Center for Metastasis Research, The University of Chicago, 5758 S Maryland Avenue, Chicago, Illinois 60637, USA.
authors.forename: Nining
authors.initials: N
authors.lastname: Guo
authors.affiliation: Department of Chemistry, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Chan
authors.affiliation: Department of Chemistry, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Poon
authors.affiliation: Department of Radiation and Cellular Oncology and The Ludwig Center for Metastasis Research, The University of Chicago, 5758 S Maryland Avenue, Chicago, Illinois 60637, USA.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.affiliation: Department of Chemistry, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D060890:B7-H1 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives; D056831:Coordination Complexes / Q000737:chemistry*; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D004339:Drug Compounding; D007109:Immunity; D007167:Immunotherapy; D007249:Inflammation / Q000473:pathology; D008055:Lipids / Q000737:chemistry; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000077150:Oxaliplatin; D010778:Photochemotherapy; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D056831:Coordination Complexes; D008055:Lipids; D009944:Organoplatinum Compounds; D011108:Polymers; D000077150:Oxaliplatin; D002734:Chlorophyll; C040298:pyropheophorbide a