2024-03-29T11:40:30Z
https://tsukuba.repo.nii.ac.jp/oai
oai:tsukuba.repo.nii.ac.jp:00025573
2022-04-27T08:53:19Z
117:811
3:62:5297:569
The ROS scavenging and renal protective effects of pH-responsive nitroxide radical-containing nanoparticles
吉冨, 徹
平山, 暁
長崎, 幸夫
Yoshitomi, Toru
Hirayama, Aki
Nagasaki, Yukio
© 2011 Elsevier Ltd.
“NOTICE: this is the author's version of a work that was accepted for publication in Biomaterials. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biomaterials, Volume 32(31),2011 DOI:10.1016/j.biomaterials.2011.07.014”
The ultimate objective of nanoparticle-based therapy is to functionalize nanomedicines in a micro-disease environment without any side effects. Here, we reveal that our pH-responsive nitroxide radical-containing nanoparticles (RNPpH) disintegrate within the renal acidic lesion and act as scavengers of reactive oxygen species (ROS), leading to a relief of acute kidney injury (AKI). RNPpH was prepared using amphiphilic block copolymers possessing 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) moieties via amine linkage as a side chain of the hydrophobic segment. The self-assembled RNPpH disintegrated at pH below 7.0 because of a protonation of the amino groups in the hydrophobic core of the nanoparticles, thereby resulting in an improvement in ROS scavenging activity. Using a renal ischemia-reperfusion AKI model in mice, the therapeutic effect of RNPpH on ROS damage was evaluated. Unlike the RNP without pH-triggered disintegration (RNPNon−pH), the RNPpH showed extremely high ROS scavenging activity and renal protective effects. It is interesting to note that the side effect of nitroxide radicals was markedly suppressed due to the compartmentalization of nitroxide radicals in the core of RNPpH in untargeted area. The morphology changes in RNPpH were confirmed by analyzing electron spin resonance spectra, and these findings provide the evidence of the real therapeutic effect of the environment-sensitive specific disintegration of nanoparticles in vivo.
Elsevier
2011-11
eng
journal article
http://hdl.handle.net/2241/114468
https://tsukuba.repo.nii.ac.jp/records/25573
21816462
10.1016/j.biomaterials.2011.07.014
0142-9612
AA00110092
Biomaterials
32
31
8021
8028
https://tsukuba.repo.nii.ac.jp/record/25573/files/Biomaterials_32-31.pdf
application/pdf
1.7 MB
2013-12-25