title: Nitroxyl radical-containing nanoparticles for novel nanomedicine against oxidative stress injury.
abstract: This article discusses the preparation and characterization of pH-sensitive nitroxyl radical-containing nanoparticles (RNPs) possessing nitroxyl radicals in the core and reactive groups on the periphery, and its biomedical application. The RNPs prepared by a self-assembling amphiphilic block copolymers composed of a hydrophilic poly(ethylene glycol) (PEG) segment and a hydrophobic poly(chloromethylstyrene) (PCMS) segment in which the chloromethyl groups were converted to 2,2,6,6-tetramethylpiperidinyloxyls (TEMPOs) via an amination of PEG-b-PCMS block copolymer with 4-amino-TEMPO are initially described. The cumulant average diameter of an RNP is approximately 40 nm, and the RNP has intense electron paramagnetic resonance signals. RNPs show a prolonged blood circulation time by the compartmentalization of nitroxyl radicals into the hydrophobic core, and disintegrate in response to a low pH environment, such as ischemic tissue, resulting in effectively scavenging reactive oxygen species due to an exposure of nitroxyl radicals from the RNP core. Thus, the RNP prepared was found to be effective for cerebral ischemia-reperfusion injury. Therefore, RNPs are promising as high-performance therapeutic nanomedicine for oxidative stress injuries.
authors.affiliation: Tsukuba Research Center for Interdisciplinary Materials Science (TIMS), University of Tsukuba, Ibaraki, 305-8573, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshitomi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D003497:Cyclic N-Oxides / Q000737:chemistry; D051379:Mice; D008823:Micelles; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage*; D009589:Nitrogen Oxides / Q000737:chemistry*; D018384:Oxidative Stress / Q000502:physiology; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy*; D013343:Styrenes / Q000737:chemistry
chemical_list: D003497:Cyclic N-Oxides; D008823:Micelles; D009589:Nitrogen Oxides; D011108:Polymers; D013343:Styrenes; C548836:chloromethylstyrene; C015527:4-amino-TEMPO; D011092:Polyethylene Glycols; C039900:nitroxyl