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 (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.

Programmed Release of Dihydroartemisinin for Synergistic Cancer Therapy Using a CaCO3 Mineralized Metal–Organic Framework

“…[17] Thet ransmission electron microscopy (TEM) images revealed that the NMOF has au niform nanoshuttle morphology with the sizes of about 258 AE 43 nm in length and 96 AE 13 nm in width ( Figure 1a;see Figure S1 in the Supporting Information). [17] Thet ransmission electron microscopy (TEM) images revealed that the NMOF has au niform nanoshuttle morphology with the sizes of about 258 AE 43 nm in length and 96 AE 13 nm in width ( Figure 1a;see Figure S1 in the Supporting Information).…”

Nanoscale Metal‐Organic Frameworks: Synthesis, Biocompatibility, Imaging Applications, and Thermal and Dynamic Therapy of Tumors

“…For example, Liu et al have used the mixture of methanol and DMF as solvent to construct nanoscale NH 2 ‐MIL‐125(Ti) through the interaction between Ti(OC 4 H 9 ) 4 and NH 2 ‐BDC (BDC: 1,4‐benzenedicarboxylic acid) in an airtight reactor at 150 °C within 24 h . Lin and co‐workers have chosen a solvent containing DMF and formic acid (FA) to synthesize Fe‐TBP nanorice with the length of 100 nm (TBP: 5,10,15,20‐tetra( p ‐benzoato)porphyrin) by the reaction between [Fe 3 O(OAc) 6 (H 2 O) 3 ]OAc (OAc = acetate) and H 4 TBP at 80 °C for 24 h . In addition to choosing different solvents, their concentration or the ratio of the mixed solvents is also crucial, which may affect the morphology of the synthesized products.…”

“…a) Nanorice morphology of Fe‐TBP. Reproduced with permission . Copyright 2018, American Chemical Society.…”

“…In view of that tumor hypoxia usually limits the efficiency of immunogenic photodynamic therapy, Lin and co‐workers proposed a new strategy by combining the Fe 3 O clusters and TBP ligand to construct Fe‐TBP NMOF‐based PS ( Figure a) . Fe 3 O catalyzed the production of oxygen to relieve hypoxia, TBP could be used to promote the conversion of oxygen to singlet oxygen, then the Fe‐TBP‐mediated PDT caused systemic anti‐tumor immunity, which could improve the αPD‐L1 immune checkpoint blockade for inducing the significant expression of cytotoxic T cells (CD 4+ and CD 8+ ).…”

“…a) Schematic illustration of using Fe‐TBP to overcome hypoxia for PDT‐primed cancer immunotherapy . Copyright 2018, American Chemical Society.…”