| 研究実績の概要 |
We developed new theranostic nanoparticles, based on quantum dots (QDs), conjugated with multispin nitroxide-cyclodextrins (QD@CD-TEMPO and QD@CD-TEMPOH) and triphenylphosphonium (TPP). Both sensors are applicable for quantitative imaging assays of oxidative stress and redox-status of living cells and tissues.
These nanoparticles combine 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.
The analytical tests using both sensors were validated by conventional redox analyses (mitoSOX, DHE, DCF, TAC).
Both sensors were applied for:
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.
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