Surface coating directed cellular delivery of TAT-functionalized quantum dots

TAT peptide functionalized shell-core ZnS-CdSe quantum dots (QDs) have been prepared by three different methods, direct ligand exchange with cysteine-terminated TAT (TAT-QD_{lig exch}), and covalent conjugation to QDs coated with silanes (TAT-QD_silica) and polyacrylate derivatives (TAT-QD_polyacrylate). The silica and polyacrylate coatings incorporated multiple primary and secondary amines, introducing positive surface charges onto the QDs, providing high water solubility and sites for peptide conjugation, while inducing the "proton sponge effect". The different coating methods produced particles of different sizes, surface charges, and colloidal stability; these factors jointly influenced the cellular uptake and subcellular localization of these particles. As the particle size increased, (TAT-QD_{lig exch} (6 nm) < TAT-QD_silica (10 nm) < QD_polyacrylate (25 nm)), both the particle surface charge and cellular uptake increased. The smaller TAT-QD_{lig exch} and TAT-QD _silica particles were localized mainly in the perinuclear regions, while the larger TAT-QD_polyacrylate particles were localized in both the perinuclear regions and the lysosomes. Compared to the other TAT-QDs, TAT-QD_lig-exch has a lower colloidal stability and was more cytotoxic due to the weak binding of the ligands.