Subcellular organelle-specific nanoparticles for simultaneous tumor targeting, imaging, and drug delivery are of enormous interest in cancer therapy. Herein, we report a selective mitochondria-targeting probe 1, which was synthesized by incorporating a triphenyl phosphine with a cyanostilbene and a long alkyl chain moiety. Probe 1 was found to display fluorescence via aggregation-induced emission (AIE). The low molecular-weight cyanostilbene-based probe 1, with and without an anticancer drug, formed a narrow homogeneous nanorod with ca. 110 nm of length or nanoparticles with ca. 20 nm diameter in aqueous media. The self-assembled cyanostilbene nanoparticles (N1) selectively accumulated in the mitochondria of cancer cells and emitted fluorescence. N1 was also able to deliver an anticancer drug, doxorubicin (DOX), to the mitochondria with high efficiency. More importantly, N1 exhibited highly selective cytotoxicity for cancer cells over normal cells. The great potential applications of this self-assembled nanoparticle to biological systems result from its ability to aggregate in the mitochondria. This aggregation led to a significant increase in the generation of intracellular reactive oxygen species and to a decrease in the mitochondrial membrane potential in cancer cells. Furthermore, tumor tissue uptake experiments in mice proposed that the self-assembled N1 had the ability to internalize and deliver the anticancer drug into tumor tissues effectively. Moreover, both N1 and N1-encapsulated doxorubicin (N1-DOX) effectively suppressed tumor growth in a xenograft model in vivo. Taken together, our findings indicate that applications of N1 as a mitochondrial targeting probe, drug delivery platform, and chemotherapeutic agent provide a unique strategy for potential image-guided therapy as well as a site-specific delivery system to cancer cells.

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来源于线粒体的自三苯基til共轭的氰基苯乙烯的线粒体靶向自组装纳米粒子能够实现位点特异性成像和抗癌药物递送

用于同时靶向肿瘤，成像和药物递送的亚细胞器特异性纳米颗粒在癌症治疗中引起了极大的兴趣。在本文中，我们报告了选择性线粒体靶向探针1，该探针是通过将三苯基膦与氰基苯乙烯和长烷基链部分结合而合成的。发现探针1通过聚集诱导发射（AIE）显示荧光。具有和不具有抗癌药的低分子量氰基噻吩基探针1形成了一个狭窄的均质纳米棒，具有 长度为110 nm或纳米粒子的长度约为 在水性介质中的直径为20 nm。自组装的氰基茂金属纳米颗粒（N1）选择性地聚集在癌细胞的线粒体中并发出荧光。N1还能够向线粒体高效递送抗癌药阿霉素（DOX）。更重要的是，相对于正常细胞，N1对癌细胞表现出高度选择性的细胞毒性。这种自组装纳米颗粒在生物系统中的巨大潜在应用是由于其在线粒体中聚集的能力。这种聚集导致癌细胞内细胞内活性氧的产生显着增加，并导致线粒体膜电位降低。此外，在小鼠中进行的肿瘤组织摄取实验表明，自组装的N1具有将抗癌药物有效地内化并将其递送到肿瘤组织中的能力。此外，在体内异种移植模型中，N1和N1封装的阿霉素（N1-DOX）均可有效抑制肿瘤的生长。综上所述，我们的发现表明N1作为线粒体靶向探针，药物递送平台和化学治疗剂的应用为潜在的图像引导疗法以及针对癌细胞的位点特异性递送系统提供了独特的策略。