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New strategies for bioconjugation to quantum dots. Study of protein-nucleic acids and protein-protein interactions using fluorescence resonance energy transfer through quantum-dot-protein conjugates

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Quantum dots in biomedicine

Water-soluble quantum dots (QDs) are emerging as important tools in bioimaging and sensing applications due to their photophysical characteristics. A group of European scientists are attempting the conjugation of QDs with biological molecules for delivery to cells.


QDs are semiconductor nanoparticles made from cadmium/selenide (Cd/Se) or cadmium telluride (Cd/Te) with a shell of zinc sulphide (ZnS). Their excellent spectroscopic properties have opened up new applications of QDs in the biomedical field. However, any improvement in the solubility properties of QDs requires efficient chemoselective methods of bioconjugation. Based on this, the EU-funded QDS project aims to develop methodologies for efficient functionalisation of QDs with complex biomolecules such as proteins and nucleic acids. Researchers will apply straightforward chemoselective reactions to allow the covalent modification of QDs at neutral pH and sub-millimolar concentrations of the peptide targets. By using positively charged amino acids, polyprolines and hydrophobic tails, scientists wish to achieve efficient cellular uptake and endosomal escape — major challenges in nanoparticle delivery. Scientists used hydrazone ligation reactions, validated in peptide–peptide and peptide–dye conjugations, to enable controlled covalent conjugation of QDs with biomolecules. The utility of this new functionalisation method has been demonstrated by carrying out enzymatic photoluminescence assays with either trypsin or chymotrypsin and the ligated peptide on the QD. Additionally, the Wittig reaction is being explored as a means of peptide conjugation to QD. As proof-of-principle, QDS researchers have performed a series of conjugations on myoglobin of different peptides or substrates. A major project achievement has been the discovery that QDs conjugated with a particular peptide have the capacity to enter the cells rapidly and get released 48 hours later. This technology could be implemented for the development and delivery of nanoparticles to inactivate specific targets in altered cells.

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