Encapsulating Quantum Dots in Lipid-PEG Micelles and Subsequent Copper-Free Click Chemistry Bioconjugation

The utility of quantum dots (QDs) for biological applications is predicated on stably dispersing the particles in aqueous media. During transfer from apolar organic solvents to water, the optical properties of the fluorescent nanoparticles must be maintained; additionally, the resulting colloid should be monodisperse and stable against aggregation. Furthermore, the hydrophilic coating should confer functional groups or conjugation handles to the QDs, as biofunctionalization is often critical to biosensing and bioimaging applications. Micelle encapsulation is an excellent technique for conferring hydrophilicity and conjugation handles to QDs. One interesting conjugation handle that can easily be added to the QDs is an azide group, which conjugates to strained alkynes via strain promoted azide-alkyne cycloaddition (SPAAC) reactions. SPAAC, or copper-free click chemistry, utilizes very mild reaction conditions, involves reactive groups that are bio-orthogonal, and is nearly quantitative. Micelle encapsulation is also very mild and preserves the optical properties of the QDs nearly perfectly. The combination of these approaches comprises a mild, effective, and straightforward approach to preparing functionalized QDs for biological applications.