Nitroxyl Radical-Containing Nanoparticles for Novel Nanomedicine Against Oxidative Stress Injury

Abstract

This article discusses the preparation and characterization of pH-sensitive nitroxyl radical-containing nanoparticles (RNPs) possessing nitroxyl radicals in the core and reactive groups on the periphery, and its biomedical application. The RNPs prepared by a self-assembling amphiphilic block copolymers composed of a hydrophilic poly(ethylene glycol) (PEG) segment and a hydrophobic poly(chloromethylstyrene) (PCMS) segment in which the chloromethyl groups were converted to 2,2,6,6-tetramethylpiperidinyloxyls (TEMPOs) via an amination of PEG-b-PCMS block copolymer with 4-amino-TEMPO are initially described. The cumulant average diameter of an RNP is approximately 40 nm, and the RNP has intense electron paramagnetic resonance signals. RNPs show a prolonged blood circulation time by the compartmentalization of nitroxyl radicals into the hydrophobic core, and disintegrate in response to a low pH environment, such as ischemic tissue, resulting in effectively scavenging reactive oxygen species due to an exposure of nitroxyl radicals from the RNP core. Thus, the RNP prepared was found to be effective for cerebral ischemia–reperfusion injury. Therefore, RNPs are promising as high-performance therapeutic nanomedicine for oxidative stress injuries.

Keywords::

• antioxidant
• bioimaging
• cerebral ischemia–reperfusion injury
• core shell-type nanoparticles
• nitroxyl radical
• oxidative stress
• reactive oxygen species

Financial & competing interests disclosure

Part of these studies were supported by Grant-in-Aid for Scientific Research (A), No.21240050, The Ministry of Education, Culture, Sports, Science, and Technology-Japan (MEXT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgements

The works described in this review were mainly carried out by our group. The authors would like to thank Professors Aki Hirayama (Tsukuba Universiy of Technology), Hirofumi Matsui (University of Tsukuba), Akira Matsumura (University of Tsukuba), Kensuke Suzuki (Dokkyo Medical University), Hideo Tsurushima (University of Tsukuba), Takashi Mamiya (University of Tsukuba), Aiki Marushima (University of Tsukuba), Daisuke Miyamoto (University of Tsukuba) and Kazuko Toh (University of Tsukuba) for collaboration in this research.

Additional information

Funding

Part of these studies were supported by Grant-in-Aid for Scientific Research (A), No.21240050, The Ministry of Education, Culture, Sports, Science, and Technology-Japan (MEXT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.