Research Institute for Electronic Science, Hokkaido University, Kita-20 Nishi-10, Kita-ku, Sapporo 001-0020, Japan.
Nanoscale. 2017 Dec 7;9(47):18690-18698. doi: 10.1039/c7nr06310e.
It has been known for decades that intracellular redox reactions control various vital functions in living systems, which include the synthesis of biomolecules, the modulation of protein functions, and cell signaling. Although there have been several reports on the control of such functions using DNA and RNA, the non-invasive optical control of biological functions is an important ongoing challenge. In this study, a hybrid of an electron donor-acceptor linked molecule based on a ferrocene(Fc)-porphyrin(ZnP)-fullerene(C) analogue and an elaborately designed nano-carrier, referred to herein as a MITO-Porter, resulted in a successful photoinduced intermolecular electron transfer reaction via the long-lived intramolecular charge separation, leading to site-specific reductive reactions in the mitochondria of living HeLa cells. A Fc-ZnP-C linked molecule, 1-Oct, was designed and prepared for taking advantage of the unique photophysical properties with excellent efficiency (i.e. a long lifetime and a high quantum yield) for photoinduced charge separation. The targeted delivery of 1-Oct to mitochondria was accomplished by using a combination of the Fc-ZnP-C molecule and a drug delivery nano-carrier, MITO-Porter, that was recently established by our group for intracellular cargo delivery. The successful delivery of 1-Oct by the MITO-Porter permitted the optically-controlled generation of O in the mitochondria of HeLa cells and the following induction of apoptosis as a cell signalling response was observed in confocal laser microscopy experiments. The obtained results indicate the use of an electron donor-acceptor system such as this can be a promising tool for the non-invasive triggering of redox-coupled cellular activities in living systems.
几十年来，人们已经知道细胞内的氧化还原反应控制着生命系统中的各种重要功能，包括生物分子的合成、蛋白质功能的调节和细胞信号转导。尽管已有几篇关于使用 DNA 和 RNA 控制这些功能的报道，但非侵入性的生物功能光学控制仍然是一个重要的持续挑战。在这项研究中，一种基于二茂铁（Fc）-卟啉（ZnP）-富勒烯（C）类似物的电子给体-受体连接分子与精心设计的纳米载体（称为 MITO-Porter）的混合物导致了通过长寿命的分子内电荷分离成功进行光诱导的分子间电子转移反应，从而导致活 HeLa 细胞线粒体中的特异性还原反应。设计并制备了一种 Fc-ZnP-C 连接分子 1-Oct，以利用其独特的光物理性质，具有优异的光诱导电荷分离效率（即长寿命和高量子产率）。通过使用我们最近为细胞内货物输送而建立的 Fc-ZnP-C 分子和药物输送纳米载体 MITO-Porter 的组合，实现了 1-Oct 向线粒体的靶向输送。MITO-Porter 成功输送 1-Oct 使得可以在 HeLa 细胞的线粒体中光控生成 O，并且在共聚焦激光显微镜实验中观察到作为细胞信号响应的随后诱导凋亡。所得结果表明，这种电子给体-受体系统的使用可以成为在活系统中非侵入性触发氧化还原偶联细胞活性的有前途的工具。
