title: The behavior of ROS-scavenging nanoparticles in blood.
abstract: Here, we report an interaction between blood and redox nanoparticles, prepared by self-assembly of amphiphilic block copolymers possessing 2,2,6,6-tetramethylpiperidine-N-oxyls as a side chain of hydrophobic segment. When 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl was added to rat whole blood, its electron spin resonance signal disappeared rapidly. In contrast, the signal from redox nanoparticles remained for a long period of time, indicating that nitroxide radicals were protected in the blood by their compartmentalization in the core of nanoparticle. Although most 2,2,6,6-tetramethylpiperidine-N-oxyls were located in the nanoparticle core, reactive oxygen species-scavenging activity was found outside of blood cells. For example, redox nanoparticles suppressed superoxide anion-induced hemolysis effectively, while 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl did not. It was revealed that redox nanoparticles were not internalized into the healthy blood cells, which was in sharp contrast to 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl. Due to its internalization into healthy platelets, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl induced mitochondrial dysfunction, while redox nanoparticles did not. Redox nanoparticles suppressed platelet adhesion and extended blood coagulation time, in contrast to 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl. These results indicate that redox nanoparticles scavenge reactive oxygen species outside of cells, but do not interfere with normal redox reactions inside of the cell. Based on these results, we determine that an anti-oxidative strategy based on nanotechnology is a rational and safe therapeutic approach.
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshitomi
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan ; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan ; Satellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
keywords: blood activation; mitochondrial dysfunction; nitroxide radicals; reactive oxygen species; redox nanoparticle