Mitochondria targeted phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has excelled as an effective approach among other non-specific techniques for its high selectivity, non-invasiveness and low systemic toxicity. Derivatives of porphyrins, indocyanine dyes and rhodamine are widely utilized for cancer PDT or PTT. However, limitations, such as hypoxia and heat resistance of PDT and PTT, have restricted their efficacy in tumor treatment, making it urgent to develop highly efficient theranostic agents with synergistic effects. Aza-boron-dipyrromethene (aza-BODIPY) has shown promising prospects for synergistic phototherapy due to its outstanding reactive oxygen species (ROS) generation and photothermal effect. Herein, we designed and synthesized a near-infrared (NIR) aza-BODIPY derivative MeOABBr (Φ_Δ = 84%). By encapsulating it with polyethylene glycol–folic acid (PEG–FA) and polyethylene glycol–triphenylphosphonium (PEG–TPP), tumor and mitochondria dual targeting nanoparticles (FMAB NPs) have been obtained. Triggered by NIR irradiation, FMAB NPs could generate ROS and hyperthermia (η = 40%) to cause mitochondrial dysfunction, resulting in cell apoptosis. Simultaneously, FMAB NPs, with unique optical properties, can be monitored precisely by photoacoustic, fluorescence and photothermal imaging in vivo. In particular, as proved by both in vitro and in vivo experiments, tumor-mitochondria dual targeted FMAB NPs exhibit high phototherapeutic efficacy without toxicity to normal tissues.

中文翻译：

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肿瘤线粒体双重靶向基于aza-BODIPY的纳米热敏剂，用于多模式成像引导光疗†

线粒体靶向光疗，包括光动力疗法（PDT）和光热疗法（PTT），因其高选择性，无创性和低系统毒性而成为其他非特异性技术中的有效方法。卟啉，吲哚菁染料和若丹明的衍生物被广泛用于癌症PDT或PTT。但是，PDT和PTT的低氧和耐热性等局限性限制了它们在肿瘤治疗中的功效，因此迫切需要开发出具有协同作用的高效治疗剂。氮杂硼二吡咯亚甲基（aza-BODIPY）由于其杰出的活性氧（ROS）产生和光热效应而显示出协同光疗的前景广阔。本文中，我们设计并合成了近红外（NIR）氮杂-BODIPY衍生物MeOABBr（Φ _Δ = 84％）。通过用聚乙二醇-叶酸（PEG-FA）和聚乙二醇-三苯基phosph（PEG-TPP）封装，获得了肿瘤和线粒体双重靶向纳米颗粒（FMAB NPs）。FMAB NPs受到NIR辐射的触发而可能产生ROS和热疗（η = 40％），从而引起线粒体功能障碍，从而导致细胞凋亡。同时，具有独特光学特性的FMAB NP可以通过体内的光声，荧光和光热成像精确监控。特别是，如通过证明在体外和体内在实验中，线粒体双重靶向的FMAB NPs具有很高的光疗功效，而对正常组织没有毒性。