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Nanoscale Metal-Organic Framework Overcomes Hypoxia for Photodynamic Therapy Primed Cancer Immunotherapy.

ABSTRACT: 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 (?-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.

SUBMITTER: Lan G

PROVIDER: S-EPMC6533908 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Nanoscale Metal-Organic Framework Overcomes Hypoxia for Photodynamic Therapy Primed Cancer Immunotherapy.

Lan Guangxu G Ni Kaiyuan K Xu Ziwan Z Veroneau Samuel S SS Song Yang Y Lin Wenbin W

Journal of the American Chemical Society 20180423 17

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 an ...[more]

PMID: 29665677

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