Ning Juewei, Huang Baozhan, Wei Zeliang, Li Wen'en, Zheng Huajie, Ma Limei, Xing Zhihua, Niu Hai, Huang Wen
Institute for Nanobiomedical Technology and Membrane Biology, Laboratory of Ethnopharmacology, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Regenerative Medicine Research Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Mol Med Rep. 2017 Jun;15(6):3761-3766. doi: 10.3892/mmr.2017.6451. Epub 2017 Apr 10.
The future of personalized cancer treatments relies on the development of functional agents that have tumor-targeted anticancer activities and can be detected in tumors using imaging. However, application of these functional agents in the clinic has been limited due to inefficient drug delivery, low specificity for tumor imaging, development of drug resistance, low signal-to-noise ratio and safety concerns regarding potential toxicity. Currently, the most common strategy to develop these functional agents is to conjugate therapeutic agents with the appropriate fluorescent probe. The present study synthesized a novel mitochondria-targeted heptamethine cyanine (Cy) derivative Cy‑triphenylphosphonium. The newly developed compound exhibited stronger near infrared (NIR) fluorescence and reacted with bovine serum albumin. In addition, it preferentially accumulated in the mitochondria of cancer cells, as observed using confocal microscopy, and efficiently reduced cancer cell viability (IC50=3.04 µM). This novel multifunctional heptamethine Cy derivative, with cancer mitochondria targeting and NIR fluorescence imaging, may be promising as an alternative anticancer agent.
个性化癌症治疗的未来依赖于开发具有肿瘤靶向抗癌活性且能够通过成像在肿瘤中被检测到的功能性药物。然而，由于药物递送效率低下、肿瘤成像特异性低、耐药性的产生、低信噪比以及对潜在毒性的安全性担忧，这些功能性药物在临床上的应用受到了限制。目前，开发这些功能性药物最常见的策略是将治疗药物与合适的荧光探针偶联。本研究合成了一种新型的线粒体靶向七甲川花菁（Cy）衍生物Cy-三苯基膦。新开发的化合物表现出更强的近红外（NIR）荧光，并与牛血清白蛋白发生反应。此外，通过共聚焦显微镜观察发现，它优先积聚在癌细胞的线粒体中，并有效降低癌细胞活力（IC50 = 3.04 μM）。这种具有癌症线粒体靶向和近红外荧光成像功能的新型多功能七甲川Cy衍生物，有望成为一种替代性抗癌药物。
