Abstract
Reactive oxygen species (ROS) are highly reactive molecules containing oxygen, which cause strong oxidative damage to lipid, protein, nucleic acid, etc. Excessive generation of ROS in the biological system leads to an increase in oxidative stress, which is a possible risk factor for systemic diseases such as arteriosclerosis, diabetes, renal failure, Alzheimer's disease, and myocardial infarction. ROS scavenging activity has become important to suppress the aggravation of local inflammation, as well as to prevent the progression of systemic diseases via penetration of ROS from the site of inflammation. Nitroxide radical compounds such as 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) catalytically scavenge ROS such as superoxide anion and hydroxyl radical and prevent the propagation of an ROS-dependent reaction. However, the diffusion of low-molecular-weight (LMW) compounds in the entire body is one of the most important factors that cause various adverse effects. For example, normal ATP-based energy would not be obtained if the mitochondrial electron transport chain is inhibited by LMW antioxidants such as TEMPO. To address these issues, we have focused on redox polymer therapeutics as a key form of nanomedicine, viz., we have developed a nitroxide-radical-containing nanoparticle (RNPN), a core-shell type of self-assembling polymeric micelle using poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene] (PEG-b-PMNT) diblock copolymer in aqueous media. The developed RNPN had a suppressive effect on oxidative stress in an in vitro study, and showed a therapeutic effect against cerebral and myocardial ischemia reperfusion injuries and intracerebral hemorrhage after intravenous administration. It should be noted that RNPN tends to avoid non-specific diffusion of nitroxide radicals to the entire body, especially important electron-transporting systems in the mitochondria.
