| 研究実績の概要 |
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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