有效干预肿瘤细胞的能量代谢，同时激活体内免疫系统进行免疫攻击对于肿瘤治疗非常有意义。然而，精确的靶向治疗仍然是一个巨大的挑战。在此，开发了一种线粒体靶向的光治疗诊断系统，FE-T纳米粒子（FE-T NPs），用于破坏肿瘤细胞中的线粒体并改变肿瘤免疫抑制微环境。FE-T NPs通过封装近红外（NIR）吸收光敏剂IR-FE-TPP在两亲性共聚物DSPE-SS-PEG-COOH中制备而成，具有同时线粒体靶向、近红外II（NIR-II）荧光成像、光热治疗（PTT）/光动力治疗（PDT）/免疫治疗（IMT）的高性能。在肿瘤治疗中，共聚物中的二硫键可以被过量的胱氨酸（GSH）水解以释放IR-FE-TPP并在线粒体中积累。经过808nm的照射，FE-T NPs的线粒体定位产生了活性氧（ROS）和高热，导致线粒体功能障碍、光诱导凋亡和免疫细胞死亡（ICD）。值得注意的是，通过FE-T NPs的线粒体靶向在体内增强了PDT / PTT，从而提高了对优异的抗肿瘤免疫反应的高效ICD。FE-T NPs为成像引导的肿瘤治疗提供了一种有效的线粒体靶向光治疗纳米平台。©2023 Wiley-VCH GmbH。

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial-targeting phototheranostic system, FE-T nanoparticles (FE-T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE-T NPs are engineered by encapsulating the near-infrared (NIR) absorbed photosensitizer IR-FE-TPP within amphiphilic copolymer DSPE-SS-PEG-COOH for high-performing with simultaneous mitochondrial-targeting, near-infrared II (NIR-II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR-FE-TPP and accumulate in mitochondria. After 808 nm irradiation, the mitochondrial localization of FE-T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial-targeting with FE-T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE-T NPs provide an effective mitochondrial-targeting phototheranostic nanoplatform for imaging-guided tumor therapy.© 2023 Wiley-VCH GmbH.