College of Chemistry and Molecular Engineering , Peking University , Beijing 100871 , China.
J Am Chem Soc. 2018 May 2;140(17):5670-5673. doi: 10.1021/jacs.8b01072. Epub 2018 Apr 23.
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.
免疫疗法已成为一种有前途的癌症治疗方法，但仅对一部分癌症患者有效。免疫原性光动力疗法（PDT）可以启动癌症免疫疗法，以提高反应率，但它的疗效受到肿瘤缺氧的严重限制。在这里，我们报告了一种纳米级金属-有机骨架 Fe-TBP，作为一种新型的纳米光敏剂，可克服肿瘤缺氧并敏化有效的 PDT，为癌症免疫疗法启动非炎症性肿瘤。Fe-TBP 由铁氧簇和卟啉配体构建而成，可在常氧和缺氧条件下敏化 PDT。Fe-TBP 介导的 PDT 显著提高了抗程序性死亡配体 1（α-PD-L1）治疗的疗效，并在结直肠癌的小鼠模型中引发了远隔效应，导致肿瘤消退超过 90%。机制研究表明，Fe-TBP 介导的 PDT 诱导了肿瘤浸润性细胞毒性 T 细胞的显著增加。
