Ultrasound-triggered nitric oxide release platform based on energy transformation for targeted inhibition of pancreatic tumor
Ultrasound-triggered nitric oxide release platform based on energy transformation for targeted inhibition of pancreatic tumor
复制标题
基于能量转化的超声触发一氧化氮释放平台靶向抑制胰腺肿瘤
DOI：
10.1021/acsnano.6b04921
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发表时间：
2016
期刊：
影响因子：
17.1
通讯作者：
Hangrong Chen
中科院分区：
文献类型：
--
作者：
Kun Zhang;Huixiong Xu;Xiaoqing Jia;Yu Chen;Ming Ma;Liping Sun;Hangrong Chen
受到在各种疾病中巨大应用潜力的启发，一氧化氮（NO）受到越来越多的关注。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、穿透深度浅、触发物电离辐射强等，这些都阻碍了临床应用。在此，使用天然精氨酸作为NO供体和局部超声作为触发器构建了超声波触发的NO按需释放系统。聚焦超声可以通过超声机械能到化学能的能量转换，激活H2O2，产生更多氧化能力比H2O2更强的含氧物种（ROS），氧化LA，从而产生更多的NO，最终抑制高度侵袭性和致死性的Panc-1肿瘤。此外，还建立了血管-细胞间基质-细胞“中继”靶向策略，并依靠该策略，在Panc-1皮下异种移植小鼠模型中NO释放系统的保留率提高了7倍以上，从而导致更明显的抑制效果和延长的生存率（60天生存率提高80%±5%）。
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 naturall-arginine as NO donor and local ultrasound as trigger. The focused ultrasound can activate H2O2to generate more oxygen-contained species (ROS) of stronger oxidation ability than H2O2for oxidizing LAviathe 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).