Synthesis and Utilization of α-Substituted Nitroxides

Yamasaki, Toshihide; Mito, Fumiya; Matsuoka, Yuta; Yamato, Masayuki; Yamada, Kenichi

doi:10.5772/39163

Cited by 2 publications

(2 citation statements)

References 43 publications

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“…Ascorbic acid exists in vivo in concentration from μM to mM depending on the type of tissue. When nitroxide radicals are applied to in vivo MRI, they are known to be reduced to the diamagnetic hydroxylamines by ascorbic acid, resulting in significantly weakening the MRI contrast [28][29][30]. For example, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), one of the most typical water-soluble nitroxide radical, is reduced quickly to hydroxylamine in the presence of ascorbic acid [14,[31][32][33][34][35][36].…”

Section: Resultsmentioning

confidence: 99%

Size-tunable MRI-visible nitroxide-based magnetic mixed micelles: preparation, stability, and theranostic application

et al. 2019

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Metal-free magnetic mixed micelles (mean diameter: 16 nm) composed of biocompatible surfactant Tween 80 and hydrophobic pyrrolidine-N-oxyl radical were prepared by mixing them in phosphate-buffered saline. The magnetic mixed micelles were characterized by dynamic light scattering and small angle neutron scattering measurements. The stability of the micelles is found to depend on the length of alkyl side chain in the nitroxide compounds and degree of unsaturation in the hydrophobic chain in the surfactant. The size of the mixed micelle can be tuned by changing the molar ratio of Tween 80 and nitroxyl radical. In view of theranostic application of the micelle, the cytotoxicity and stability in a physiological environment was investigated; the mixed micelle exhibited no cytotoxicity, high colloidal stability and high resistance towards reduction by large excess ascorbic acid. The in vitro and in vivo magnetic resonance imaging (MRI) revealed sufficient contrast enhancement in the proton longitudinal relaxation time (T 1 ) weighted images. In addition, hydrophobic fluorophores and an anticancer drug are stably encapsulated in the mixed micelles and showed fluorescence (FL) upon reduction by ascorbic acid and cytotoxicity to cancer cells, respectively. For example, the paclitaxel-loaded mixed micelles efficiently suppressed cancer cell growth. Furthermore, they were found to give higher MRI contrast (higher r 1 value) in vitro than the micelles without paclitaxel. The magnetic mixed micelles presented here are promising theranostic agents in nanomedicine due to their high biocompatibility and high resistivity towards reduction as well as functioning as a drug carrier in therapy and MR or FL imaging probe in diagnosis.

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Section: Resultsmentioning

confidence: 99%

Size-tunable MRI-visible nitroxide-based magnetic mixed micelles: preparation, stability, and theranostic application

et al. 2019

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“…When nitroxide radicals were applied to the in vivo MRI measurement, radical reduction occurred and resulted in a significant decrease in the MRI contrast [33,34,35]. For example, 2,2,6,6-tetramethylpiperidine- N -oxyl (TEMPO) derivatives, such as 4-oxo-2,2,6,6-tetramethylpiperidine- N -oxyl (TEMPONE) and 4-hydroxy-2,2,6,6-tetramethylpiperidine- N -oxyl (TEMPOL), were reduced rapidly (half-life ( τ 1/2 ) < 2 min) to the corresponding hydroxylamines in the presence of ascorbic acid [36]. In our molecular design, we expected that the interplay between four long hydrophilic tails in 2 and four neighboring substituents in 4 14 should enhance the reduction resistance to ascorbic acid sterically.…”

Section: Resultsmentioning

confidence: 99%

Magnetic Mixed Micelles Composed of a Non-Ionic Surfactant and Nitroxide Radicals Containing a d-Glucosamine Unit: Preparation, Stability, and Biomedical Application

et al. 2019

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Metal-free magnetic mixed micelles (mean diameter: < 20 nm) were prepared by mixing the biocompatible non-ionic surfactant Tween 80 and the non-toxic, hydrophobic pyrrolidine-N-oxyl radicals bearing a d-glucosamine unit in pH 7.4 phosphate-buffered saline (PBS). The time-course stability and in vitro magnetic resonance imaging (MRI) contrast ability of the mixed micelles was found to depend on the length of the alkyl chain in the nitroxide radicals. It was also confirmed that the mixed micelles exhibited no toxicity in vivo and in vitro and high stability in the presence of a large excess of ascorbic acid. The in vivo MRI experiment revealed that one of these mixed micelles showed much higher contrast enhancement in the proton longitudinal relaxation time (T1) weighted images than other magnetic mixed micelles that we have reported previously. Thus, the magnetic mixed micelles presented here are expected to serve as a promising contrast agent for theranostic nanomedicines, such as MRI-visible targeted drug delivery carriers.

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Synthesis and Utilization of α-Substituted Nitroxides

Cited by 2 publications

References 43 publications

Size-tunable MRI-visible nitroxide-based magnetic mixed micelles: preparation, stability, and theranostic application

Size-tunable MRI-visible nitroxide-based magnetic mixed micelles: preparation, stability, and theranostic application

Magnetic Mixed Micelles Composed of a Non-Ionic Surfactant and Nitroxide Radicals Containing a d-Glucosamine Unit: Preparation, Stability, and Biomedical Application

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