Abstract
To image inflammation sites, we developed a novel nanoparticle, hydroxylamine-containing nanoparticle (HANP), which emits an intense electron spin resonance (ESR)-signal triggered by enzymatic oxidation reaction and pH-sensitive self-disintegration. The nanoparticle was prepared from an amphiphilic block copolymer, poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-1-hydroxyl)aminomethylstyrene] (PEG-b-PMNT-H), which spontaneously forms a core-shell type polymeric micelle (particle diameter = ca. 50 nm) in aqueous media. Because the PMNT-H segment in the block copolymer possesses amino groups in each repeating unit, the particle can be disintegrated by protonation of the amino groups in an acidic pH environment such as inflammation sites, which is confined to the hydrophobic core of HANP. Mixing HANP with horseradish peroxidase (HRP)/H(2)O(2) mixture resulted in enzymatic oxidization of the hydroxylamines in the PEG-b-PMNT-H and converted the hydroxylamine to the stable nitroxide radical form in PEG-b-poly[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)aminomethylstyrene] (PEG-b-PMNT), which shows an intense ESR signal. It is interesting to note that the ESR signal increased at a greater rate under acidic conditions (pH 5.6) than that under neutral conditions (pH 7.4), although the enzymatic activity of HRP under neutral conditions is known to be much higher than that under acidic conditions. This indicates that enzymatic oxidation reaction was accelerated by synchronizing the disintegration of HANP under acidic conditions. On the basis of these results, HANP can be used as a high-performance ESR probe for imaging of inflammation sites.
Highlights
Inflammation is strongly related to various disorders and diseases such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease [1]
To image inflammation sites, we developed a novel nanoparticle, hydroxylamine-containing nanoparticle (HANP), which emits an intense electron spin resonance (ESR)-signal triggered by enzymatic oxidation reaction and pH-sensitive self-disintegration
We developed a nitroxide radical-containing nanoparticle (RNP) for use as a nanomedicine for oxidative stress injury [16,17,18,19,20] and as a bioimaging nanoprobe for magnetic resonance imaging (MRI) and electron spin resonance imaging (ESRI) [21], which is composed of a poly(ethylene glycol)-b-poly(methylstyrene) block copolymer possessing TEMPO moieties via an amine linkage (PEG-b-PMNT) [22]
Summary
Inflammation is strongly related to various disorders and diseases such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease [1]. Tumors are known to develop at chronic inflammation sites, and inflammatory cells have been shown to be present in biopsied samples from tumors [2, 3]. A non-invasive imaging probe for detecting inflammation at an early and subclinical stage is important for decisions related to the necessity of therapy and subsequent prediction of outcomes and for diagnostics of several diseases including cancer. To image an inflamed area, a probe with a high signal-to-background ratio is desirable. Promising strategies to improve the signalto-background ratio include ‘‘specific accumulation of probe at the inflamed area’’ and ‘‘on–off regulation of signal’’, in which the imaging probe ideally has no signal in the non-target tissue and is activated at the inflamed area
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
