OxyStressSens: Quantum dot@Multi-spin-cyclodextrin sensor for mapping of oxidative stress in cells using EPR and optical imaging

The best strategy of fighting “free radical diseases” (as cancer, neurodegeneration, atherosclerosis, etc.) is an effective early stage diagnosis. This study proposes a new concept to realize revolutionary class contrast agents to be applied as sensitive probes for detection of “oxidative stress” during development and progression of different pathologies, by using optical and magnetic resonance imaging techniques.We developed a new “oxidative stress” sensor (OxiStressSens) based on conjugation of quantum dots with multi-nitroxide-functionalized cyclodextrin. The oxidation of nitroxide residues to their radical form was accompanied by strong quenching of quantum dot fluorescence and appearance of high EPR contrast. In opposite, the reduction of nitroxide residues in their hydroxylamine form was accompanied by rapid decay of EPR signal and appearance of strong fluorescence signal. Thus, OxyStressSens allows evaluation of the balance between reducers/oxidizers and level of “oxidative stress”. Besides the large magnetic moment or high quantum yield, the dimension of OxiStressSens and its positive charge ensure enhance permeability and retention effect in cells and tissues. The sensor enters into viable cells, which was visualized by EPR and fluorescent imaging. OxyStressSens was applied for detection of “oxidative stress” in cell suspensions, treated by rotenone and 2-methoxyestradiol – a combination, inducing mitochondrial dysfunction, overproduction of superoxide and mild or severe oxidative damages. The physicochemical characteristics and easy cell permeability give a reason to believe that the sensor will be appropriate for in vivo imaging. Since the T1-weigheted MRI contrast of nitroxides follows the same dynamics as their EPR contrast, the sensor is applicable also for nitroxide-enhanced MRI studies.Acknowledgements: This study was supported by the Japanese Society for Promotion of Science (JSPS), Grant-in-aid “Kakenhi C”.ISER-450th International Conference on Nanoscience, Nanotechnology & Advanced Materials (IC2NAM-2018

Precise Size Control and Synchronized Synthesis of Six Colors of CdSe Quantum Dots at a Slow-Increasing Temperature Gradient

The present study describes a simultaneous and highly reproducible large-scale synthesis of six (and more) colors of size-homogeneous and highly luminescent CdSe quantum dots in a single reaction, controlled by a slow-increasing temperature gradient. The described protocol allows a precise control and a synchronized isolation of aliquots of CdSe nanocrystals with defined sizes, avoiding disturbance of the growth of nanocrystals (existing in the reaction mixture) to the isolation of the next aliquot. The obtained quantum dot fractions are of high quality (in 95% size-homogeneous) and have sharp photoluminescence spectra (fwhm ~ 30 nm), quantum yields of 45-70% (in organic solvent), and a lack of aggregation in organic solvents. The method is environmentally friendly as it ensures almost complete utilization of the precursors and productive yield ~95%

Assessment of renal function by 7T MRI and prototype of contrast agent - Experimental model

The present study shows that nitroxide derivative (carbamoyl-PROPXYL) is suitable 1H-MRI contrast probe for visualization of hypercholesterolemia-induced renal dysfunction in intact animals and clarifying the mechanism(s) of renal damage mediated by cholesterol. The probe was applied in a concentration, which was 3 times lower than the LD50 for intravenous administration in C57Bl/6 mice. Since the probe is excreted by kidneys, it could be considered harmless for mammalians in the selected dose and appropriate candidate for translational research. The data were compared with those, obtained by conventional 1H-MRI contrast agent Gd/DTPA for assessment of renal function in experimental animals and patients

Multimodal quantum dot probe for optical imaging of colon cancer,

4th European Molecular Imaging Meetin