期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 140, 期 17, 页码 5670-5673出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.8b01072
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资金
- National Cancer Institute [U01-CA198989]
- Materials Research Collaborative Access Team (MRCAT)
- U.S. DOE [DE-AC02-06CH11357]
Immunotherapy has become a promising cancer therapy, but only works for a subset of cancer patients. Immunogenic photodynamic therapy (PDT) can prime cancer immunotherapy to increase the response rates, but its efficacy is severely limited by tumor hypoxia. Here we report a nanoscale metal organic framework, Fe-TBP, as a novel nanophotosensitizer to overcome tumor hypoxia and sensitize effective PDT, priming non-inflamed tumors for cancer immunotherapy. Fe-TBP was built from iron-oxo clusters and porphyrin ligands and sensitized PDT under both normoxic and hypoxic conditions. Fe-TBP mediated PDT significantly improved the efficacy of anti-programmed death-ligand 1 (alpha-PD-L1) treatment and elicited abscopal effects in a mouse model of colorectal cancer, resulting in >90% regression of tumors. Mechanistic studies revealed that Fe-TBP mediated PDT induced significant tumor infiltration of cytotoxic T cells.
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