2019 Fiscal Year Research-status Report
New quantum biosensors for quantitative molecular imaging assays of oxidative stress
| Project/Area Number |
18K04909
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| Research Institution | National Institutes for Quantum and Radiological Science and Technology |
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Principal Investigator |
Rumiana Bakalova 国立研究開発法人量子科学技術研究開発機構, 量子生命科学領域, 主任研究員(任常) (30469936)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | Redox / Nitroxyl Radical / mitochondria |
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| Outline of Annual Research Achievements |
We developed redox-responsive quantum sensors, based on quantum dots (QDs), conjugated with multispin nitroxide-cyclodextrins (QD@CD-TEMPO & QD@CD-TEMPOH) and triphenylphosphonium (TPP), combining several features: (i) three imaging modalities (MRI, EPR, optical); (ii) intracellular delivery and localization mainly into the mitochondria due to TPP; (iii) possibility to sense and visualize the areas of oxidative stress and redox-status in living cells and tissues due to dynamics of their contrast properties, based on the balance between oxidizers and reducers; (iv) redox-modulating activity and possibility to induce apoptosis in cancer cells, without significant effect on viability of normal cells due to SOD-mimetic feature of nitroxide residues. Both sensors are applicable for quantitative imaging assays of oxidative stress and redox-status of living cells and tissues. In 2019, the following tests were done with both sensors:
1. EPR/optical imaging of oxidative stress and total reducing capacity in cultured cells with exogenously induced mitochondrial dysfunction. Cytotoxicity and induction of apoptosis on normal and cancer cells were also analysed (MTS assay, Annexin-V test). 2. MR imaging in animals with kidney dysfunction, induced by oxidative stress (pilot study only on few mice with hypercholesterolemia).
The in vitro analytical tests using both sensors were validated by conventional redox analyses (mitoSOX, DHE, DCF, TAC, mitochondrial potential assay).
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
多数の論文が出版された実績があり、また産学連携にも繋がったため
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| Strategy for Future Research Activity |
予定以上の成果を上げているため、本研究計画に沿って、今まで以上の熱意で研究を進める。
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| Causes of Carryover |
発注差額が生じたため、ごくわずかな残が生じた。計画に変更は無く、来年度、消耗品費に繰り入れる。
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