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Mitochondria-Targeted Small-Molecule Fluorophores for Dual Modal Cancer Phototherapy

机译：线粒体靶向小分子荧光团的双模式癌症光疗法。

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摘要

Mitochondria are recognized as the ideal target for cancer treatment because they play a central role in oxidative metabolism and apoptosis. In this work, a mitochondria-targeted near-infrared (NIR) photosensitizer (PS) for synchronous cancer photodynamic therapy (PDT) and photothermal therapy (PTT) is synthesized. This multifunctional small-molecule PS is developed from a variety of synthesized heptamethine cyanine dyes, which are modified with various N-alkyl side chains on the lipophilic cationic heptamethine core. It is demonstrated to preferentially accumulate in cancer cells by organic-anion transporting polypeptide mediated active transport and retain in mitochondria by its lipophilic cationic property. As mitochondria are susceptible to hyperthermia and excessive reactive oxygen species, this new PS integrating PTT and PDT treatment exhibits highly efficient phototherapy in multiple cancer cells and animal xenograft models. Furthermore, this targeted PS with NIR imaging property also enables tumors and their margins clearly visualized, providing the potential for precisely imaging-guided phototherapy and treatment monitoring. This is the first report that a small-molecule PS integrates both cancer PTT and PDT treatment by targeting mitochondria, significantly increasing the photosensitization. This work may also present a practicable strategy to develop small-molecule-based cancer theranostic agents for simultaneous cancer targeting, imaging, and therapy.
机译：线粒体被认为是治疗癌症的理想靶标，因为它们在氧化代谢和细胞凋亡中起着核心作用。在这项工作中，针对同步癌症光动力疗法（PDT）和光热疗法（PTT）的线粒体靶向近红外（NIR）光敏剂（PS）得以合成。这种多功能小分子PS是由多种合成的七甲基花青染料开发而​​成的，这些染料被亲脂性阳离子七蛋氨酸核心上的各种N-烷基侧链修饰。已证明其通过有机阴离子转运多肽介导的主动转运而优先在癌细胞中积累，并通过其亲脂性阳离子特性保留在线粒体中。由于线粒体易受高温和过多的活性氧的影响，因此这种结合了PTT和PDT治疗的新型PS在多种癌细胞和动物异种移植模型中均表现出高效的光疗效果。此外，这种具有NIR成像特性的靶向PS还可以使肿瘤及其边缘清晰可见，从而为精确成像指导的光疗和治疗监测提供了潜力。这是第一个报道，小分子PS通过靶向线粒体来整合癌症PTT和PDT治疗，从而显着提高光敏性。这项工作也可能提出一种可行的策略，以开发基于小分子的癌症治疗药物，以同时进行癌症靶向，影像和治疗。

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  • 来源
    《Advanced Functional Materials》 |2016年第17期|2826-2835|共10页
  • 作者

    Luo Shenglin; Tan Xu; Fang Shengtao; Wang Yu; Liu Tao; Wang Xin; Yuan Yi; Sun Huiqin; Qi Qingrong; Shi Chunmeng;

  • 作者单位

    Third Mil Med Univ, Dept Prevent Med, Chongqing Engn Res Ctr Nanomed, Inst Combined Injury,State Key Lab Trauma Burns &, 30th Gaotanyan St, Chongqing 400038, Peoples R China;

    Third Mil Med Univ, Dept Prevent Med, Chongqing Engn Res Ctr Nanomed, Inst Combined Injury,State Key Lab Trauma Burns &, 30th Gaotanyan St, Chongqing 400038, Peoples R China;

    Third Mil Med Univ, Dept Prevent Med, Chongqing Engn Res Ctr Nanomed, Inst Combined Injury,State Key Lab Trauma Burns &, 30th Gaotanyan St, Chongqing 400038, Peoples R China;

    Third Mil Med Univ, Dept Prevent Med, Chongqing Engn Res Ctr Nanomed, Inst Combined Injury,State Key Lab Trauma Burns &, 30th Gaotanyan St, Chongqing 400038, Peoples R China;

    Third Mil Med Univ, Dept Prevent Med, Chongqing Engn Res Ctr Nanomed, Inst Combined Injury,State Key Lab Trauma Burns &, 30th Gaotanyan St, Chongqing 400038, Peoples R China;

    Third Mil Med Univ, Dept Prevent Med, Chongqing Engn Res Ctr Nanomed, Inst Combined Injury,State Key Lab Trauma Burns &, 30th Gaotanyan St, Chongqing 400038, Peoples R China;

    Third Mil Med Univ, Coll Pharm, 30th Gaotanyan St, Chongqing 400038, Peoples R China;

    Third Mil Med Univ, Dept Prevent Med, Chongqing Engn Res Ctr Nanomed, Inst Combined Injury,State Key Lab Trauma Burns &, 30th Gaotanyan St, Chongqing 400038, Peoples R China;

    Sichuan Univ, West China Sch Pharm, Dept Med Chem, 17th Peoples South Rd, Chengdu 610041, Peoples R China;

    Third Mil Med Univ, Dept Prevent Med, Chongqing Engn Res Ctr Nanomed, Inst Combined Injury,State Key Lab Trauma Burns &, 30th Gaotanyan St, Chongqing 400038, Peoples R China;

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