Nanoscale Metal–Organic Framework Overcomes Hypoxia for Photodynamic Therapy Primed Cancer Immunotherapy
Top Cited Papers
- 18 April 2018
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 140 (17), 5670-5673
- https://doi.org/10.1021/jacs.8b01072
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 (α-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.Keywords
Funding Information
- National Cancer Institute (U01 CA198989)
This publication has 26 references indexed in Scilit:
- Shutdown!Science, 2013
- The Chemistry and Applications of Metal-Organic FrameworksScience, 2013
- Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced CancerThe New England Journal of Medicine, 2012
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerThe New England Journal of Medicine, 2012
- Light‐Triggered Theranostics Based on Photosensitizer‐Conjugated Carbon Dots for Simultaneous Enhanced‐Fluorescence Imaging and Photodynamic TherapyAdvanced Materials, 2012
- A Water‐Stable Porphyrin‐Based Metal–Organic Framework Active for Visible‐Light PhotocatalysisAngewandte Chemie, 2012
- The blockade of immune checkpoints in cancer immunotherapyNature Reviews Cancer, 2012
- Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agentsNature Materials, 2011
- A luminescent nanoscale metal–organic framework for sensing of nitroaromatic explosivesChemical Communications, 2011
- Hypoxia, angiogenesis, and colorectal cancerCurrent Colorectal Cancer Reports, 2007