Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510 (Japan).
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510 (Japan).
Angew Chem Int Ed Engl. 2015 Sep 28;54(40):11725-9. doi: 10.1002/anie.201505534. Epub 2015 Aug 6.
Controlling cell functions using external photoresponsive nanomaterials has enormous potential for the development of cell-engineering technologies and intractable disease therapies, but the former currently requires genetic modification of the target cells. We present a method using plasma-membrane-targeted gold nanorods (pm-AuNRs) prepared with a cationic protein/lipid complex to activate a thermosensitive cation channel, TRPV1, in intact neuronal cells. Highly localized photothermal heat generation mediated by the pm-AuNRs induced Ca(2+) influx solely by TRPV1 activation. In contrast, the use of previously reported cationic AuNRs that are coated with a conventional synthetic polymer also led to photoinduced Ca(2+) influx, but this influx resulted from membrane damage. Our method provides an optogenetic platform without the need for prior genetic engineering of the target cells and might be useful for novel TRPV1-targeted phototherapeutic approaches.
利用外部光响应纳米材料控制细胞功能,对于细胞工程技术和难治性疾病治疗具有巨大的潜力,但目前前者需要对目标细胞进行基因修饰。我们提出了一种使用带有阳离子蛋白/脂质复合物的质膜靶向金纳米棒(pm-AuNRs)的方法,来激活完整神经元细胞中的热敏阳离子通道 TRPV1。由 pm-AuNRs 介导的高度局域光热产生仅通过 TRPV1 激活诱导 Ca(2+)内流。相比之下,使用之前报道的带有传统合成聚合物的阳离子 AuNRs 也导致了光诱导的 Ca(2+)内流,但这种内流是由于细胞膜损伤所致。我们的方法提供了一种无需对靶细胞进行先前基因工程的光遗传学平台,可能对新型 TRPV1 靶向光疗方法有用。