Reactive Oxygen Species-Scavenging Nanomedicines for the Treatment of Oxidative Stress Injuries


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Abstract

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 (RNPN) and pH-insensitive redox nanoparticle (RNPO), 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, RNPN 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 RNPN, it shows remarkable therapeutic effects on oxidative stress injuries such as renal and cerebral ischemia–reperfusion injuries after intravenous administration. Moreover, RNPN 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 RNPO 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, RNPO 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.

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