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Photophysics of dopamine-modified quantum dots and effects on biological systems

Abstract

Semiconductor quantum dots (QDs) have been widely used for fluorescent labelling. However, their ability to transfer electrons and holes to biomolecules leads to spectral changes and effects on living systems that have yet to be exploited. Here we report the first cell-based biosensor based on electron transfer between a small molecule (the neurotransmitter dopamine) and CdSe/ZnS QDs. QD–dopamine conjugates label living cells in a redox-sensitive pattern: under reducing conditions, fluorescence is only seen in the cell periphery and lysosomes. As the cell becomes more oxidizing, QD labelling appears in the perinuclear region, including in or on mitochondria. With the most-oxidizing cellular conditions, QD labelling throughout the cell is seen. Phototoxicity results from the creation of singlet oxygen, and can be reduced with antioxidants. This work suggests methods for the creation of phototoxic drugs and for redox-specific fluorescent labelling that are generalizable to any QD conjugated to an electron donor.

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Figure 1: Spectral characteristics of two independent populations of CdSe/ZnS QDs exposed to dopamine.
Figure 2: Oxidation of QD–dopamine by EPR and transient emission spectroscopy.
Figure 3: Proposed mechanisms for observed spectral and cell-uptake properties of QD–dopamine conjugates under different environmental conditions.
Figure 4: Uptake of QD–dopamine by mammalian cells.
Figure 5: Singlet-oxygen generation and phototoxicity.
Figure 6: Redox-sensitive labelling with QD–dopamine and comparison with commercial redox sensor dye RSR.

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Acknowledgements

This research is supported by the United States EPA—Science to Achieve Results (STAR) program Grant No. R831712, and by the Canadian Institutes of Health Research (CIHR) Grant No. PPP-71486. S.J.C. acknowledges support from The Banting Research Foundation. N.M.D. is supported by the Office of Basic Energy Sciences, Division of Chemical Sciences, US-DOE under contract number W-31-109-Eng-38. The TCSPC work carried out at USC is supported by the David and Lucile Packard Foundation and NASA-JPL instrument contract 1 250 277.

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Correspondence to Jay L. Nadeau.

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Clarke, S., Hollmann, C., Zhang, Z. et al. Photophysics of dopamine-modified quantum dots and effects on biological systems. Nature Mater 5, 409–417 (2006). https://doi.org/10.1038/nmat1631

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