title: Chlorin-Based Nanoscale Metal-Organic Framework Systemically Rejects Colorectal Cancers via Synergistic Photodynamic Therapy and Checkpoint Blockade Immunotherapy.
abstract: Photodynamic therapy (PDT) can destroy local tumors and minimize normal tissue damage, but is ineffective at eliminating metastases. Checkpoint blockade immunotherapy has enjoyed recent success in the clinic, but only elicits limited rates of systemic antitumor response for most cancers due to insufficient activation of the host immune system. Here we describe a treatment strategy that combines PDT by a new chlorin-based nanoscale metal-organic framework (nMOF), TBC-Hf, and a small-molecule immunotherapy agent that inhibits indoleamine 2,3-dioxygenase (IDO), encapsulated in the nMOF channels to induce systemic antitumor immunity. The synergistic combination therapy achieved effective local and distant tumor rejection in colorectal cancer models. We detected increased T cell infiltration in the tumor microenvironment after activation of the immune system with the combination of IDO inhibition by the small-molecule immunotherapy agent and immunogenic cell death induced by PDT. We also elucidated the underlying immunological mechanisms and revealed compensatory roles of neutrophils and B cells in presenting tumor-associated antigens to T cells in this combination therapy. We believe that nMOF-enabled PDT has the potential to significantly enhance checkpoint blockade cancer immunotherapy, affording clinical benefits for the treatment of many difficult-to-treat cancers.
authors: Department of Chemistry, The University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
authors: Kuangda
authors: K
authors: Lu
authors: Department of Chemistry, The University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
authors: Chunbai
authors: C
authors: He
authors: Department of Chemistry, The University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.|Department of Radiation and Cellular Oncology and The Ludwig Center for Metastasis Research, The University of Chicago , Chicago, Illinois 60637, United States.
authors: Nining
authors: N
authors: Guo
authors: Department of Chemistry, The University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
authors: Christina
authors: C
authors: Chan
authors: Department of Chemistry, The University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
authors: Kaiyuan
authors: K
authors: Ni
authors: Department of Radiation and Cellular Oncology and The Ludwig Center for Metastasis Research, The University of Chicago , Chicago, Illinois 60637, United States.
authors: Ralph R
authors: RR
authors: Weichselbaum
authors: Department of Chemistry, The University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
authors: Wenbin
authors: W
authors: Lin
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016503:Drug Delivery Systems; D007167:Immunotherapy / Q000379:methods*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D000073396:Metal-Organic Frameworks / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009360:Neoplastic Cells, Circulating; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry*; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D000073396:Metal-Organic Frameworks; D011166:Porphyrins; D026082:Singlet Oxygen; C006969:chlorin