Design and Preparation of a Nanoprobe for Imaging Inflammation Sites

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 PEGb-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.

Liposome-like nanostructures for drug delivery

“…For example, through electrostatic interactions, polyelectrolytes can be adsorbed onto the liposome surfaces with opposite charges. 54, 55 Alternatively, hydrophilic polymer chains can be covalently conjugated to the head group of the lipids followed by the liposome formation. 56, 57 Stabilization can be also achieved within liposome bilayers by cross-linking the hydrophobic tails of the lipids.…”

Secondary Ion Mass Spectrometry Imaging of Tissues, Cells, and Microbial Systems

“…Cluster sources have also improved the three dimensional capabilities of the SIMS imaging by allowing thinner ‘slices’ to be sputtered off the sample for higher z-dimension lateral resolution. Data processing techniques (e.g., multivariate analysis) are now more commonly applied to MSI data analysis, allowing for more information to be mined from the large amount of data produced with SIMS techniques [16]. …”

ESR Method in Monitoring of Nanoparticle Endocytosis in Cancer Cells

“…Iron oxide nanomaterials are characterized using different methods, including transmission electron microscopy (TEM), X-ray diffraction (XRD), superconducting quantum interference device (SQUID), UV-vis spectroscopy, and dynamic light scattering (DLS) [14,15]. The electron spin resonance (ESR) method has previously been used for the description of the physical properties of liposomes [16,17], polymer nanoparticles [18][19][20], or graphene [21]. Indeed, ESR can be a useful method for the characterization of iron oxide nanomaterials [22][23][24][25].…”