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Macrophage-derived nitric oxide (NO) plays a critical role in atherosclerosis and presents as a potential biomarker. We assessed the uptake, distribution, and NO detection capacity of an irreversible, ruthenium-based, fluorescent NO sensor (Ru-NO) in macrophages, plasma, and atherosclerotic plaques. In vitro, incubation of Ru-NO with human THP1 monocytes and THP1-PMA macrophages caused robust uptake, detected by Ru-NO fluorescence using mass-cytometry, confocal microscopy, and flow cytometry. THP1-PMA macrophages had higher Ru-NO uptake (+13%, p < 0.05) than THP1 monocytes with increased Ru-NO fluorescence following lipopolysaccharide stimulation (+14%, p < 0.05). In mice, intraperitoneal infusion of Ru-NO found Ru-NO uptake was greater in peritoneal CD11b+F4/80+ macrophages (+61%, p < 0.01) than CD11b+F4/80− monocytes. Infusion of Ru-NO into Apoe−/− mice fed high-cholesterol diet (HCD) revealed Ru-NO fluorescence co-localised with atherosclerotic plaque macrophages. When Ru-NO was added ex vivo to aortic cell suspensions from Apoe−/− mice, macrophage-specific uptake of Ru-NO was demonstrated. Ru-NO was added ex vivo to tail-vein blood samples collected monthly from Apoe−/− mice on HCD or chow. The plasma Ru-NO fluorescence signal was higher in HCD than chow-fed mice after 12 weeks (37.9%, p < 0.05). Finally, Ru-NO was added to plasma from patients (N = 50) following clinically-indicated angiograms. There was lower Ru-NO fluorescence from plasma from patients with myocardial infarction (−30.7%, p < 0.01) than those with stable coronary atherosclerosis. In conclusion, Ru-NO is internalised by macrophages in vitro, ex vivo, and in vivo, can be detected in atherosclerotic plaques, and generates measurable changes in fluorescence in murine and human plasma. Ru-NO displays promising utility as a sensor of atherosclerosis.
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http://dx.doi.org/10.3390/biomedicines10081807 | DOI Listing |
Langmuir
November 2022
Department of Physics, National Institute of Technology Kurukshetra, Kurukshetra136119, Haryana, India.
Incorporating water-insoluble nitric oxide (NO)-releasing molecules into biocompatible vesicles may allow for the tunable control of NO release on a specific target site. In vesicles, membrane fluidity plays an important role and influences the final therapeutic efficiency of drugs loaded into the vesicles. Hence, we aimed to investigate the effect of lipid fluidity on the NO release behavior of the photo-controllable ruthenium nitrosyl (Ru-NO) complex.
View Article and Find Full Text PDFBiomedicines
July 2022
Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia.
Macrophage-derived nitric oxide (NO) plays a critical role in atherosclerosis and presents as a potential biomarker. We assessed the uptake, distribution, and NO detection capacity of an irreversible, ruthenium-based, fluorescent NO sensor (Ru-NO) in macrophages, plasma, and atherosclerotic plaques. In vitro, incubation of Ru-NO with human THP1 monocytes and THP1-PMA macrophages caused robust uptake, detected by Ru-NO fluorescence using mass-cytometry, confocal microscopy, and flow cytometry.
View Article and Find Full Text PDFInorg Chem
June 2021
Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.
How to deliver nitric oxide (NO) to a physiological target and control its release quantitatively is a key issue for biomedical applications. Here, a water-soluble nitrosylruthenium complex, [(CH)N][RuCl(5cqn)(NO)] (H5cqn = 5-chloro-8-quinoline), was synthesized, and its structure was confirmed with H NMR and X-ray crystal diffraction. Photoinduced NO release was investigated with time-resolved Fourier transform infrared and electron paramagnetic resonance (EPR) spectroscopies.
View Article and Find Full Text PDFJ Mater Chem B
August 2020
Materials Science and Engineering College, Guilin University of Technology, Key Laboratory of New Processing Technology for Nonferrous Materials, Ministry of Education, Guangxi Key Laboratory of Optical and Electronic Materials and Devices, Guangxi Collaborative Innovation Center for Exploration of Hidden Nonferrous Metal Deposits and Development of New Materials, Guilin University of Technology, 541004 Guilin, China.
Light-induced NO release based on exogenous NO donors has attracted substantial attention in clinical applications; the induction light source usually converts near-infrared light to blue or ultraviolet light. However, the low efficiency of near-infrared light-assisted chemical light energy conversion remains a challenge, especially for NaYF4:Yb3+/Tm3+ photoconverting near-infrared light to ultraviolet (UV) and blue light. In this paper, a luminescence-enhanced strategy is reported by doping Ca2+ into NaYF4:Yb3+/Tm3+ and coating it with NaGdF4 through a two-step solvothermal method.
View Article and Find Full Text PDFMater Sci Eng C Mater Biol Appl
May 2019
Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Laboratório de Química de Calixarenos, Espectroscopia Molecular e Catálise, Universidade Federal de São Paulo, Rua Prof. Arthur Riedel, 275, CEP 09972-270 Diadema, SP, Brazil. Electronic address:
Quinoline-derivative coordination compounds were synthesized with Zn(II), Al(III), Cu(II), Ru(II) producing 1-4 compounds using 5-nitro-8-hydroxyquinoline and 5-8 compounds using 5-chloro-8-hydroxyquinoline. These coordination compounds were characterized by elemental analysis and H NMR, IR, UV-Vis and fluorescence spectroscopies, representing the coherent data matched all compounds. Myelotoxicity data, as well as the biochemical data, depicted the compounds have low cytotoxicity towards the blood cells.
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