State Key Laboratory of High performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences , 1295 Dingxi Road, Shanghai 200050, P. R. China.
Department of Medical Ultrasound, Shanghai Tenth people's Hospital, Tongji University School of Medicine , 301 Yan-chang-zhong Road, Shanghai 200072, P. R. China.
ACS Nano. 2016 Dec 27;10(12):10816-10828. doi: 10.1021/acsnano.6b04921. Epub 2016 Nov 28.
Inspired by considerable application potential in various diseases, nitric oxide (NO) has gained increasing attention. Nevertheless, current NO release scaffolds suffer from some inevitable drawbacks, for example, high toxicity for NO donor byproducts, poor specificity, shallow penetration depth, and strong ionizing irradiation for triggers, all of which remain obstacles to clinical application. Herein, an ultrasound-triggered NO on-demand release system is constructed using natural l-arginine as NO donor and local ultrasound as trigger. The focused ultrasound can activate HO to generate more oxygen-contained species (ROS) of stronger oxidation ability than HO for oxidizing LA via the energy transformation from ultrasound mechanical energy to chemical energy, and thus produce more NO for ultimately suppressing the highly aggressive and lethal Panc-1 tumor. Moreover, a blood vessel-intercellular matrix-cell "relay" targeting strategy has been established and relying on it, over 7-fold higher retention of such NO release system in a subcutaneous xenograft mouse model of Panc-1 is obtained, which consequently results in a more evident inhibitory effect and a prolonged survival rate (80% ± 5% improvement in 60-day survival).
受一氧化氮（NO）在多种疾病中具有广泛应用潜力的启发，NO 受到了越来越多的关注。然而，目前的 NO 释放支架存在一些不可避免的缺点，例如，NO 供体副产物毒性高、特异性差、渗透深度浅、触发剂电离辐射强等，这些都成为临床应用的障碍。本文以天然 L-精氨酸为 NO 供体，局部超声为触发源，构建了一种超声触发的按需释放 NO 系统。聚焦超声可以通过将超声机械能转化为化学能，激活 HO 产生比 HO 更强氧化能力的含氧物种（ROS），从而通过氧化 LA 产生更多的 NO，最终抑制侵袭性强、致死性高的 Panc-1 肿瘤。此外，还建立了一种血管-细胞外基质-细胞“接力”靶向策略，基于该策略，在 Panc-1 皮下异种移植小鼠模型中，NO 释放系统的滞留率提高了 7 倍以上，从而显著提高了抑制效果和延长了存活率（60 天存活率提高了 80%±5%）。
