Quantum-dot/dopamine bioconjugates function as redox coupled assemblies for in vitro and intracellular pH sensing

Abstract

The use of semiconductor quantum dots (QDs) for bioimaging and sensing has progressively matured over the past decade. QDs are highly sensitive to charge-transfer processes, which can alter their optical properties. Here, we demonstrate that QD–dopamine–peptide bioconjugates can function as charge-transfer coupled pH sensors. Dopamine is normally characterized by two intrinsic redox properties: a Nernstian dependence of formal potential on pH and oxidation of hydroquinone to quinone by O2 at basic pH. We show that the latter quinone can function as an electron acceptor quenching QD photoluminescence in a manner that depends directly on pH. We characterize the pH-dependent QD quenching using both electrochemistry and spectroscopy. QD–dopamine conjugates were also used as pH sensors that measured changes in cytoplasmic pH as cells underwent drug-induced alkalosis. A detailed mechanism describing the QD quenching processes that is consistent with dopamine’s inherent redox chemistry is presented.

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Figure 1: Dopamine–peptide synthesis, QD conjugation, energy-transfer mechanism and cyclic voltammetry.
Figure 2: Steady-state photoluminescence spectra.
Figure 3: Excited-state lifetimes, QD absorption, oxidation and H2O2.
Figure 4: pH sensing in vitro.
Figure 5: Intracellular pH sensing.

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Acknowledgements

The authors thank T. O’Shaughnessy and I. Willner for helpful suggestions and acknowledge the CB Directorate/Physical S&T Division (DTRA), ONR, NRL and the NRL-NSI for financial support. M.H.S. acknowledges an NRC fellowship through NRL. J.B.B-C. acknowledges a Marie Curie International Outgoing Fellowship.

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I.L.M., M.H.S. and S.A.T. conceived of the experimental strategy and carried out experiments. J.B.B-C. and P.E.D. designed and synthesized the peptides used. K.S., B.C.M. and M.H.S. synthesized QD material. M.H.S. synthesized the dopamine isothiocyante. K.S. and H.M. analysed experimental results. J.B.D. grew cell cultures and assisted with cellular experiments. J.S.M. carried out fluorescence lifetime experiments.

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Correspondence to Igor L. Medintz or Hedi Mattoussi.

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The authors declare no competing financial interests.

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Medintz, I., Stewart, M., Trammell, S. et al. Quantum-dot/dopamine bioconjugates function as redox coupled assemblies for in vitro and intracellular pH sensing. Nature Mater 9, 676–684 (2010). https://doi.org/10.1038/nmat2811

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