title: Ultrasound-Triggered Nitric Oxide Release Platform Based on Energy Transformation for Targeted Inhibition of Pancreatic Tumor.
abstract: 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 H2O2to generate more oxygen-contained species (ROS) of stronger oxidation ability than H2O2for 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).
authors.affiliation: 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.|Ultrasound Research and Education Institute, Tongji University School of Medicine , 301 Yan-chang-zhong Road, Shanghai 200072, P. R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth people's Hospital, Tongji University School of Medicine , 301 Yan-chang-zhong Road, Shanghai 200072, P. R. China.|Ultrasound Research and Education Institute, Tongji University School of Medicine , 301 Yan-chang-zhong Road, Shanghai 200072, P. R. China.
authors.forename: Huixiong
authors.initials: H
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Jia
authors.affiliation: 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.
authors.forename: Yu
authors.identifier: 0000-0002-8206-3325
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth people's Hospital, Tongji University School of Medicine , 301 Yan-chang-zhong Road, Shanghai 200072, P. R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Hangrong
authors.identifier: 0000-0003-0827-1270
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D001120:Arginine; D004735:Energy Transfer; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide; D010084:Oxidation-Reduction; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000628:therapy; D014463:Ultrasonography
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D006861:Hydrogen Peroxide
keywords: Nitric oxide; Panc-1 tumor; l-arginine donor; oxygen-contained species; ultrasound trigger; “relay” targeting