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

TLDR

Immunotherapy shows promise yet only benefits a subset of patients, and photodynamic therapy can prime it but its efficacy is hampered by tumor hypoxia. The study reports Fe‑TBP, a nanoscale metal‑organic framework designed to overcome tumor hypoxia and sensitize photodynamic therapy, thereby priming non‑inflamed tumors for immunotherapy. Fe‑TBP, composed of iron‑oxo clusters and porphyrin ligands, sensitizes PDT under normoxic and hypoxic conditions and induces robust infiltration of cytotoxic T cells into tumors. Fe‑TBP mediated PDT markedly enhanced α‑PD‑L1 therapy, producing over 90 % tumor regression and abscopal effects in a colorectal cancer mouse model.

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.