Ultra-rapid transfer of oleic acid-coated hydroxyapatite nanocrystals into water via a sodium citrate-assisted ligand exchange strategy

Abstract

Precise control of the size, morphology and surface hydrophilicity of HA nanocrystals is an important prerequisite for the realization of relevant applications, especially biologically relevant ones. Although sodium oleate-assisted hydrothermal methods have received considerable attention due to their impressive synthesis quality and extremely wide aspect ratio tunability. However, the synthesized nanocrystals are usually hydrophobic due to oleic acid encapsulation, which greatly limits their wide application in biomedical fields. In view of this, we have established a robust ligand exchange strategy with sodium citrate as the exchange ligand and a mixture of water and ethanol as the exchange environment. The ligand exchange reaction requires only 5 min of stirring at 25 °C. DLS and zeta potential results show that the ligand-exchanged HA nanocrystals are highly negatively charged in water and dispersed as individual particles in water. TG and IR results showed that the oleic acid ligands on the surface of the nanocrystals were completely replaced by citric acid ligands. TEM images showed no change in the size and morphology of the nanocrystals before and after ligand exchange. Moreover, the colloidal stability of the ligand-exchanged HA nanocrystals in water could be quickly recovered in a few seconds even after freeze-drying into powder. The success of ligand exchange is mainly attributed to the fact that sodium citrate complexes calcium ions more strongly than sodium oleate, as well as the addition of ethanol eliminates the oil-water interface providing the basis for the approach of sodium citrate molecules to HA nanocrystals. This strategy undoubtedly bridges the gap that oleic acid-coated HA nanocrystals can be quickly and efficiently transferred to water, allowing HA nanocrystals to be used in bio-related applications without any obstacles.