Targeted delivery of nitric oxide via a 'bump-and-hole'-based enzyme-prodrug pair
Targeted delivery of nitric oxide via a 'bump-and-hole'-based enzyme-prodrug pair
复制标题
通过基于“凸块和孔”的酶-前药对靶向输送一氧化氮。
DOI：
10.1038/s41589-018-0190-5
复制
发表时间：
2019-02-01
影响因子：
14.8
通讯作者：
Zhao, Qiang
中科院分区：
文献类型：
--
作者：
Hou, Jingli;Pan, Yiwa;Zhao, Qiang
The spatiotemporal generation of nitric oxide (NO), a versatile endogenous messenger, is precisely controlled. Despite its therapeutic potential for a wide range of diseases, NO-based therapies are limited clinically due to a lack of effective strategies for precisely delivering NO to a specific site. In the present study, we developed a novel NO delivery system via modification of an enzyme-prodrug pair of galactosidase-galactosyl-NONOate using a 'bump-and-hole' strategy. Precise delivery to targeted tissues was clearly demonstrated by an in vivo near-infrared imaging assay. The therapeutic potential was evaluated in both rat hindlimb ischemia and mouse acute kidney injury models. Targeted delivery of NO clearly enhanced its therapeutic efficacy in tissue repair and function recovery and abolished side effects due to the systemic release of NO. The developed protocol holds broad applicability in the targeted delivery of important gaseous signaling molecules and offers a potent tool for the investigation of relevant molecular mechanisms.
