缺氧作为肿瘤的固有特征，与光动力疗法（PDT）临床效果不佳密切相关，因为缺氧会导致活性氧（ROS）生产力无法有效根除肿瘤。在这项研究中，通过将IR780和OXPHOS抑制剂阿托伐醌（ATO）封装在三苯基膦（TPP）改性的聚（乙二醇）甲醚-嵌段聚中，制备了一种氧化磷酸化（OXPHOS）靶向纳米平台，以缓解缺氧并增强PDT性能(L-丙交酯-乙交酯) (mPEG-PLGA) 纳米载体 (TNPs/IA)。 ATO 通过中断 OXPHOS 中的电子转移来抑制肿瘤细胞的线粒体呼吸，从而节省氧气来产生 ROS。受益于TPP的线粒体靶向功能，ATO直接递送至其作用位点，以较低的剂量获得显着的效果。此外，将光敏剂IR780定位到线粒体（一种更容易受到ROS影响的细胞器）是一种有前途的方法，可以减轻ROS因其半衰期短和扩散半径窄而造成的时空限制。因此，TNPs/IA 表现出精确的亚细胞定位，通过损伤线粒体导致 ATP 产生崩溃，并在 HeLa 皮下异种移植模型中通过氧增强 PDT 产生显着的抗肿瘤功效。总体而言，TNPs/IA 是光动力根除肿瘤的一种潜在策略。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Hypoxia as an inherent feature in tumors is firmly associated with unsatisfactory clinical outcomes of photodynamic therapy (PDT) since the lack of oxygen leads to ineffective reactive oxygen species (ROS) productivity for tumor eradication. In this study, an oxidative phosphorylation (OXPHOS) targeting nanoplatform was fabricated to alleviate hypoxia and enhance the performance of PDT by encapsulating IR780 and OXPHOS inhibitor atovaquone (ATO) in triphenylphosphine (TPP) modified poly(ethylene glycol) methyl ether-block-poly(L-lactide-co-glycolide) (mPEG-PLGA) nanocarriers (TNPs/IA). ATO by interrupting the electron transfer in OXPHOS could suppress mitochondrial respiration of tumor cells, economising on oxygen for the generation of ROS. Benefiting from the mitochondrial targeting function of TPP, ATO was directly delivered to its site of action to obtain highlighted effect at a lower dosage. Furthermore, positioning the photosensitizer IR780 to mitochondria, a more vulnerable organelle to ROS, was a promising method to attenuate the spatiotemporal limitation of ROS caused by its short half-life and narrow diffusion radius. As a result, TNPs/IA exhibited accurate subcellular localization, lead to the collapse of ATP production by damaging mitochondrion and elicited significant antitumor efficacy via oxygen-augmented PDT in the HeLa subcutaneous xenograft model. Overall, TNPs/IA was a potential strategy in photodynamic eradication of tumors.Copyright © 2024 Elsevier B.V. All rights reserved.