缺氧的肿瘤微环境和单一机制严重限制了共价有机骨架（COF）纳米颗粒在癌症治疗中的光动力治疗（PDT）效率。在这里，我们提出了一种载铁、亲水性1,2-二硬脂酰-sn-glycero-3-磷酸乙醇胺-N-[甲氧基（聚乙二醇）-2000] (DSPE-PEG2000)-修饰的空心共价有机框架 (HCOF)、Fe-HCOF-PEG2000，由于其 I 型和 II 型光动力学，可用于缺氧 PDT 和铁死亡治疗具有半导体聚合物和微孔骨架的Fe-HCOF-PEG2000纳米颗粒（Fe-HCOFs-PEG2000）具有高效的光物理特性。此外，Fe-HCOF-PEG2000 上的铁纳米颗粒会引起铁死亡，并在常氧和缺氧条件下进一步增强肿瘤消除。 DSPE-PEG2000赋予Fe-HCOF-PEG2000亲水性，使其能够在血供丰富的器官，尤其是肿瘤中循环和积累。 808 nm NIR 激活 Fe-HCOF-PEG2000 在肿瘤中聚集，并在缺氧下显着抑制肿瘤生长。据我们所知，Fe-HCOF-PEG2000 是 I/II 型 PDT 和铁死亡的领先组合。这种纳米材料的强大抗肿瘤作用预示着作为肿瘤纳米治疗药物的临床转化前景。© 2024 Peng et al.

The hypoxic tumor microenvironment and single mechanisms severely limit the photodynamic therapy (PDT) efficiency of covalent organic framework (COF) nanoparticles in cancer treatment.Here, we propose an iron-loaded, hydrophilic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000)-modified hollow covalent organic framework (HCOF), Fe-HCOF-PEG2000, for use in hypoxic PDT and ferroptosis therapy owing to its type I and II photodynamic ability and iron nanoparticle loading property.Fe-HCOF-PEG2000 nanoparticles (Fe-HCOFs-PEG2000) with semiconducting polymers and microporous skeletons allow efficient photophysical properties. Moreover, the iron nanoparticles on Fe-HCOF-PEG2000 caused ferroptosis and further enhanced tumor elimination under normoxic and hypoxic conditions. DSPE-PEG2000 endowed Fe-HCOF-PEG2000 with hydrophilicity, allowing it to circulate and accumulate in organs rich in blood supply, especially tumors. 808 nm NIR activated Fe-HCOF-PEG2000 aggregated in tumors and significantly inhibited tumor growth under hypoxia.To our knowledge, Fe-HCOF-PEG2000 is the leading combination of type I/II PDT and ferroptosis. The strong antitumor effects of this nanomaterial suggest prospects for clinical translation as a tumor nanotherapy drug.© 2024 Peng et al.