New quantum biosensors for quantitative molecular imaging assays of oxidative stress

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K04909
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 28040:Nanobioscience-related
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Bakalova Rumiana 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所・分子イメージング診断治療研究部, 主任研究員(任常) (30469936)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: redox / Nitroxide / MRI / EPR / 蛍光イメージング / センサー / 量子ドット

Outline of Final Research Achievements

We developed two-set Qdot sensors for tracking total redox capacity and/or oxidative stress in living biological objects using EPR, MRI, and optical imaging: (i) QD@CD-TEMPO, and (ii) QD@CD-TEMPOH. Both sensors are composed of small-size QDs, coated with paramagnetic CD-TEMPO or diamagnetic CD-TEMPOH conjugated with triphenylphosphonium (TPP) groups. The TPP groups achieve intracellular delivery and mitochondrial localization. Nitroxide residues interact simultaneously with various oxidizers and reducers, and the sensors are transformed from paramagnetic form into diamagnetic form and vice-versa due to nitroxide redox cycling. Sensors were applied for EPR/optical imaging of intracellular redox-status in vitro on isolated cells with different proliferative indexes, as well as for noninvasive MRI of severe oxidative stress in vivo on mice with renal dysfunction. Details are described in Anal Chem 2021 and press-released.

Free Research Field

生物化学

Academic Significance and Societal Importance of the Research Achievements

Chemical structures are original. They allow analysis of intracellular superoxide in absolute units, which is impossible using conventional fluorescent/luminescent probes. Sensors are appropriate for diagnostics and control of therapy of free-radical diseases.