Chen Dapeng, Zhang Jiaojiao, Tang Yunyun, Huang Xiaoyu, Shao Jinjun, Si Weili, Ji Jun, Zhang Qi, Huang Wei, Dong Xiaochen
Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211800, China.
J Mater Chem B. 2018 Jul 21;6(27):4522-4530. doi: 10.1039/c8tb01347k. Epub 2018 Jun 29.
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 = 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.
线粒体靶向光疗，包括光动力疗法（PDT）和光热疗法（PTT），作为一种有效的方法，因其高选择性、非侵入性和低全身毒性，在其他非特异性技术中表现出色。卟啉、吲哚菁染料和罗丹明的衍生物被广泛用于癌症的PDT或PTT。然而，PDT和PTT的局限性，如缺氧和耐热性，限制了它们在肿瘤治疗中的疗效，因此迫切需要开发具有协同效应的高效诊疗剂。氮杂硼二吡咯亚甲基（aza-BODIPY）由于其出色的活性氧（ROS）生成和光热效应，在协同光疗方面显示出广阔的前景。在此，我们设计并合成了一种近红外（NIR）氮杂硼二吡咯亚甲基衍生物MeOABBr（Φ = 84%）。通过用聚乙二醇-叶酸（PEG-FA）和聚乙二醇-三苯基膦（PEG-TPP）对其进行封装，获得了肿瘤和线粒体双靶向纳米颗粒（FMAB NPs）。在近红外光照射下，FMAB NPs可产生活性氧和热疗（η = 40%），导致线粒体功能障碍，从而引起细胞凋亡。同时，具有独特光学性质的FMAB NPs可在体内通过光声、荧光和光热成像进行精确监测。特别是，体外和体内实验均证明，肿瘤-线粒体双靶向FMAB NPs具有高光疗效果，且对正常组织无毒。
