Reactive oxygen species-scavenging nanomedicines for the treatment of oxidative stress injuries.
This Progress Report describes a development of two types of reactive oxygen species (ROS)-scavenging nanomedicines for the treatment of oxidative stress injuries, referred to as pH-sensitive redox nanoparticle (RNP(N) ) and pH-insensitive redox nanoparticle (RNP(O) ), which are prepared by self-assembling amphiphilic block copolymers possessing nitroxide radicals as a side chain of hydrophobic segment via amine and ether linkages, respectively. Due to a protonation of amino groups in hydrophobic core, RNP(N) disintegrates in low pH environments such as ischemic, inflamed, and tumor tissues, resulting in increased ROS-scavenging activity because of the exposed nitroxide radicals from the core. Utilizing pH-responsiveness of RNP(N) , it shows remarkable therapeutic effects on oxidative stress injuries such as renal and cerebral ischemia-reperfusion injuries after intravenous administration. Moreover, RNP(N) shows an enhancement of the activity of anticancer drugs by suppression of activation of transcription factors in tumor due to the ROS scavenging. On the other hand, orally administered RNP(O) has notable characteristics such as preferential accumulation in mucosa and inflamed area of gastrointestinal tract and no uptake into blood stream. Based on these characters, RNP(O) shows a remarkable therapeutic effect for the gastrointestinal inflammation without any adverse effects. Thus, ROS-scavenging nanomedicines have therapeutic efficacy in numerous oxidative stress diseases.
Department of Chemistry, Graduate School of Science, The University of Tokyo, Bunkyo-ku 7-3-1, Tokyo, 113-0033, Japan.
Toru
T
Yoshitomi
Yukio
Y
Nagasaki
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009589:Nitrogen Oxides / Q000737:chemistry; D010084:Oxidation-Reduction; D011108:Polymers / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry* / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D013113:Spin Labels
D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; D004337:Drug Carriers; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D011108:Polymers; D017382:Reactive Oxygen Species; D013113:Spin Labels; C039900:nitroxyl; C001803:tempol
anti-inflammation; nitroxide radicals; oxidative stress; reactive oxygen species; redox nanoparticles