受载氧材料生物相容性差、氧负荷性能不理想、细胞耗氧量异常高导致缺氧缓解不足等制约，肿瘤缺氧干预方式的临床转化仍达不到预期。本文精心开发了一种基于模块化氟化前药设计和共组装纳米技术的无载流子氧纳米罐，该纳米罐通过焦脱镁叶绿酸a（PPa）氟化前药（FSSP）的分子纳米组装和耗氧量轻松制备而成。抑制剂（阿托伐醌，ATO）。纳米罐巧妙地实现了足够的富氧，同时抑制肿瘤内的耗氧量，从而彻底缓解肿瘤缺氧。重要的是，FSSP 中的氟化模块不仅使 FSSP 和 ATO 具有良好的共组装性，而且还使纳米组件能够轻松携带氧气。正如预期的那样，它表现出优异的携氧能力、良好的药代动力学、按需激光触发 ATO 释放、闭环肿瘤缺氧缓解以及体外和体内 PPa 介导的 PDT 显着增强。这项研究为肿瘤缺氧干预增强癌症治疗提供了一种新颖的纳米治疗范例。© 2024 作者。 《Advanced Science》由 Wiley‐VCH GmbH 出版。

The clinical translation of tumor hypoxia intervention modalities still falls short of expectation, restricted by poor biocompatibility of oxygen-carrying materials, unsatisfactory oxygen loading performance, and abnormally high cellular oxygen consumption-caused insufficient hypoxia relief. Herein, a carrier-free oxygen nano-tank based on modular fluorination prodrug design and co-assembly nanotechnology is elaborately exploited, which is facilely fabricated through the molecular nanoassembly of a fluorinated prodrug (FSSP) of pyropheophorbide a (PPa) and an oxygen consumption inhibitor (atovaquone, ATO). The nano-tank adeptly achieves sufficient oxygen enrichment while simultaneously suppressing oxygen consumption within tumors for complete tumor hypoxia alleviation. Significant, the fluorination module in FSSP not only confers favorable co-assemblage of FSSP and ATO, but also empowers the nanoassembly to readily carry oxygen. As expected, it displays excellent oxygen carrying capacity, favorable pharmacokinetics, on-demand laser-triggerable ATO release, closed-loop tumor hypoxia relief, and significant enhancement to PPa-mediated PDT in vitro and in vivo. This study provides a novel nanotherapeutic paradigm for tumor hypoxia intervention-enhanced cancer therapy.© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.