Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 3, Pages 1108-1112Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201911429
Keywords
antigen presentation; checkpoint blockade immunotherapy; CpG delivery; metal-organic frameworks; photodynamic therapy
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Funding
- National Cancer Institute [U01-CA198989, 1R01CA216436]
- University of Chicago Medicine Comprehensive Cancer Center [NIH CCSG: P30 CA014599]
- Division of Chemistry (CHE), National Science Foundation [NSF/CHE-1346572]
- Division of Materials Research (DMR), National Science Foundation [NSF/CHE-1346572]
- U.S. DOE [DE-AC02-06CH11357]
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Checkpoint blockade immunotherapy (CBI) awakes a host innate immune system and reactivates cytotoxic T cells to elicit durable response in some cancer patients. Now, a cationic nanoscale metal-organic framework, W-TBP, is used to facilitate tumor antigen presentation by enabling immunogenic photodynamic therapy (PDT) and promoting the maturation of dendritic cells (DCs). Comprised of dinuclear W-VI secondary building units and photosensitizing 5,10,15,20-tetra(p-benzoato)porphyrin (TBP) ligands, cationic W-TBP mediates PDT to release tumor associated antigens and delivers immunostimulatory CpG oligodeoxynucleotides to DCs. The enhanced antigen presentation synergizes with CBI to expand and reinvigorate cytotoxic T cells, leading to superb anticancer efficacy and robust abscopal effects with >97 % tumor regression in a bilateral breast cancer model.
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