| Literature DB >> 30598545 |
Jingli Hou1,2, Yiwa Pan3, Dashuai Zhu4, Yueyuan Fan1, Guowei Feng5, Yongzhen Wei3, He Wang3, Kang Qin3, Tiechan Zhao6, Qiang Yang7, Yan Zhu6, Yongzhe Che4, Yangping Liu2, Jiansong Cheng8, Deling Kong3, Peng George Wang9, Jie Shen10, Qiang Zhao11,12.
Abstract
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.Entities:
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Year: 2018 PMID： 30598545 DOI： 10.1038/s41589-018-0190-5
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040