Design and characterization of lysine cross-linked mercapto-acid biocompatible quantum dots

Semiconductor quantum dots (QDs) are a new generation of inorganic probes with advantageous properties over traditional organic-only probes for biological applications. A major hurdle in the use of QDs for biology is the inability of the hydrophobically synthesized QDs to interface with aqueous environments. There have been tremendous advances in the surface modification of hydrophobic QDs. However, none of the current techniques fits all of the criteria for an ideal QD coating for biological applications (e.g., maintain the small size and optical properties of QDs, have low nonspecific binding) while providing cost-effective, easy preparation on a large scale. We developed a highly stable biocompatible coating for the surface of ZnS-capped CdSe QDs that maintains all of the hydrophobic-coated QD optical properties. These QDs are prepared by first coating them with mercaptoundecanoic acid and are further cross-linked with the amino acid lysine in the presence of dicyclohexylcarbodiimide to form a stable hydrophilic shell. The surface contains carboxylic acid and amino functional groups for conjugation to biomolecules. Using a dynamic light scattering method, we found that the hydrodynamic diameter of these surface-modified QDs is approximately 20 nm. We demonstrated the feasibility of preparing >400 mg of the biocompatible QDs and the successful conjugation of proteins onto their surface. Finally, we characterized the QD stability and optical properties in various biologically relevant environments.