A mechanism to signal receptor–substrate interactions with luminescent quantum dots

Abstract

Semiconductor quantum dots are becoming valuable analytical tools for biomedical applications. Indeed, their unique photophysical properties offer the opportunity to design luminescent probes for imaging and sensing with unprecedented performance. In this context, we have identified operating principles to transduce the supramolecular association of complementary receptor-substrate pairs into an enhancement in the luminescence of sensitive quantum dots. Our mechanism is based on the electrostatic adsorption of cationic quenchers on the surface of anionic quantum dots. The adsorbed quenchers suppress efficiently the emission character of the associated nanoparticles on the basis of photoinduced electron transfer. In the presence of target receptors able to bind the quenchers and prevent electron transfer, however, the luminescence of the quantum dots is restored. Thus, complementary receptor-substrate pairs can be identified with luminescence measurements relying on our design logic. In fact, we have demonstrated with a representative example that our protocol can be adapted to signal protein-ligand interactions.electron transfer ͉ luminescent chemosensors ͉ nanoparticles ͉ proteinligand interactions S emiconductor quantum dots are inorganic nanoparticles with remarkable photophysical properties (1-5). In particular, their one-and two-photon absorption cross-sections, luminescence lifetimes, and photobleaching resistances are significantly greater than those of conventional organic fluorophores. Furthermore, their broad absorption bands extend continuously from the UV to the visible region of the electromagnetic spectrum and, therefore, offer a vast selection of possible excitation wavelengths. Instead, their narrow emission bands can be positioned precisely within the visible and near-infrared regions with fine adjustments of their physical dimensions. In fact, pools of quantum dots with different diameters can be designed to emit in parallel at different wavelengths after excitation at a single wavelength, offering the opportunity to implement unprecedented multichannel assays.Organic dyes do not offer the unique collection of attractive photophysical properties associated with semiconductor quantum dots. Indeed, it is becoming apparent that these inorganic nanoparticles can complement, if not replace, their organic counterparts in a diversity of biomedical applications (6-12). Nonetheless, decades of intensive investigations on the structure and properties of organic chromophores have indicated valuable strategies to design sensitive fluorescent probes able to signal the presence of target analytes with changes in emission intensity (13-16). Their operating principles generally rely on the covalent connection of a fluorescent component to a receptor unit. The receptor is engineered to quench the emission of the fluorophore on the basis of either electron or energy transfer. The supramolecular association of the receptor with a complementary analyte, however, suppresses the quenching mechanism and leads to a si...

Semiconductor Quantum Dots for Bioanalysis

“…A common method for FRET-based sensing of an analyte involves the displacement of a bound quencher. [81] For example, the association of maltose to the hybrid composed of the maltose-binding protein was examined by the application of a CdSe/ZnS QD linked to the maltose binding protein (MBP). [39] These particles were interacted with a b-cyclodextrin-QSY-9 dye conjugate, resulting in the quenching of the QDs luminescence (Figure 8 A).…”

Quantum Dots in Bioanalysis: A Review of Applications across Various Platforms for Fluorescence Spectroscopy and Imaging

“…11 In addition to sensing configurations that use hole accepting metal complexes to quench QD PL, there are examples that use electron accepting molecules, such as quinones, to monitor enzyme activity 199,200 and intracellular pH, 183 or bipyridinium, to monitor receptor-substrate interactions. 180 Initially, Yildiz et al electrostatically adsorbed a bipyridinium dye to the surface of QDs and found that a macrocyclic receptor, cucurbit [7]uril, could disrupt the CT quenching interaction through competitive host-guest interactions. 180 Cui et al reversed this approach by modifying CdTe QDs with thiolated cucurbit [6]uril (CB [6]) via self-assembly.…”

“…180 Initially, Yildiz et al electrostatically adsorbed a bipyridinium dye to the surface of QDs and found that a macrocyclic receptor, cucurbit [7]uril, could disrupt the CT quenching interaction through competitive host-guest interactions. 180 Cui et al reversed this approach by modifying CdTe QDs with thiolated cucurbit [6]uril (CB [6]) via self-assembly. 201 The CB [6] improved the colloidal stability of the QDs and, more pertinently, bound a nitrobenzene amine electron acceptor through a host-guest interaction, providing the proximity needed for CT quenching.…”

Enzyme-Conjugated CdSe/ZnS Quantum Dot Biosensors for Glucose Detection

“…14) Through combining with receptors such as proteins or DNA and detachment from the QD surface, the PL intensity was partially recovered and the amount of PL peak intensity was used as a measure of glucose concentration. 15,16) In this study, we report another effective design of PL glucose biosensors using CdSe/ZnS QDs, organic acid and glucose oxidase (GOx). We measured the increase in the PL peak intensity through the transfer of electrons occurring during the enzymatic oxidation reaction to the conduction band of the QDs.…”