Effective Reduction of Nonspecific Binding by Surface Engineering of Quantum Dots with Bovine Serum Albumin for Cell-Targeted Imaging

Abstract

Quantum dots (QDs) have been widely used as fluorescent probes in cell-targeted imaging. However, nonspecific binding to cellular membranes has been a major challenge. In this study, a new approach is developed for effective reduction of nonspecific binding by bovine serum albumin (BSA)-coated QDs in cell targeting. The experimental results show efficient transfer of hydrophobic QDs from organic to aqueous phase in the presence of BSA aqueous solution under ultrasonication. This ultrasonication-based approach is facile, rapid, and efficient. Stabilization of QDs is mainly achieved by multiple mercapto groups in BSA macromolecules as multidentate ligands and partially by hydrophobic interaction between BSA and pending fatty ligands on QDs. The water solubility of QDs is enhanced by the surface amino and carboxyl groups, which also provide reaction sites for conjugation of targeting ligands. The BSA-coated QDs, with an overwhelming majority of hydrodynamic diameter size of ca. 18 nm, are colloidally stable under both acidic and basic conditions and found to exhibit strong fluorescent intensities. The nonspecific cellular binding is effectively reduced by BSA-coated QDs, compared with the mercaptopropionic acid (MPA)-coated CdTe QDs. BSA-coated QDs are further functionalized with cyclic Arg-Gly-Asp (cRGD) peptide. The cell assays indicate their high target-selectivity in integrin α(v)β(3)-expressed cell imaging.