College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, 510640, China.
Small. 2014 Sep 24;10(18):3750-60. doi: 10.1002/smll.201400437. Epub 2014 May 15.
The therapeutic applications of exogenous nitric oxide are usually limited by its short half-life and its vulnerability to many biological substances, thus straightforward and precise spatiotemporal control of NO delivery may be critical to its therapeutic effects. Herein, the mitochondria-targeted and photoresponsive NO-releasing nanosystem is demonstrated as a new approach for cancer treatment. The nanosystem is fabricated by covalently incorporating a NO photo-donor and a mitochondria targeting ligand onto carbon-dots; accordingly, multi-functionalities (mitochondria-targeting, light-enhanced efficient NO-releasing, and cell imaging) are achieved. The in vitro NO release profiles for the nanosystem show that the duration of NO release from the present C-dot-based nanosystem containing immobilized SNO can be extended up to 8 hours or more. Upon cellular internalization, the nanosystem can target mitochondria and release NO. The action of the nanosystem on three cancer cell lines is evaluated; it is found that the targeted NO-releasing system can cause high cytotoxicity towards the cancer cells by specifically damaging their mitochondria. Additionally, light irradiation can amplify the cell apoptosis by enhancing NO release. These observations demonstrate that incorporating mitochondria-targeting ligand onto a NO-releasing system can enhance its pro-apoptosis action, thereby providing new insights for exploiting NO in cancer therapy.
外源性一氧化氮的治疗应用通常受到其半衰期短和易受许多生物物质影响的限制，因此直接、精确的时空控制 NO 的释放可能对其治疗效果至关重要。在此，展示了一种基于线粒体靶向和光响应的一氧化氮释放纳米系统，作为一种新的癌症治疗方法。该纳米系统是通过将一氧化氮光供体和线粒体靶向配体共价结合到碳点上来制备的；因此，实现了多功能性（靶向线粒体、光增强高效 NO 释放和细胞成像）。纳米系统的体外 NO 释放曲线表明，本研究中含有固定 SNO 的基于 C 点的纳米系统的 NO 释放持续时间可以延长至 8 小时或更长时间。在细胞内化后，纳米系统可以靶向线粒体并释放 NO。评估了纳米系统对三种癌细胞系的作用；发现靶向 NO 释放系统可以通过特异性损伤癌细胞的线粒体而对癌细胞产生高细胞毒性。此外，光照射可以通过增强 NO 释放来放大细胞凋亡。这些观察结果表明，将线粒体靶向配体结合到 NO 释放系统中可以增强其促凋亡作用，从而为利用 NO 进行癌症治疗提供了新的见解。
