Post-synthetic citrate modification of Eu(iii) doped hydroxyapatite nanoparticles for enhanced cellular uptake in bioimaging applications

Abstract

Interest in the development of various innovative synthesis approaches for producing biomimetic nanoparticles (NPs) arises from their remarkable ability to achieve effective cellular uptake for various biomedical applications. In this study, citrate, one of the main organic constituents of natural bone, serves as an efficient post-synthetic surface modifier for Eu(III)-doped hydroxyapatite nanoparticles (Eu:HAp NPs), enabling effective functionalization of the as-synthesized material. The as-prepared (both bare and citrate-modified) Eu:HAp NPs are characterized by various analytical techniques like XRD, FTIR, FESEM, TEM, and DLS. Characterization studies indicated that this synthesis method alters only the surface characteristic properties, while the core structural properties of the particles remain unaffected. FTIR and DLS–zeta potential studies reveal that citrate modification occurs on the NP surface via chemisorption, inducing negatively charged carboxylate (COO⁻) sites and improving colloidal stability. Interestingly, citrate modification does not affect the photoluminescent emission characteristics of the as-prepared NPs. Additionally, biocompatibility and cell-imaging properties are analyzed to evaluate the effect of citrate modification of NPs on cellular uptake capacity. Both bare and citrate-modified Eu:HAp NPs do not show any significant toxicity toward HEK-293 and MDA-MB-231 cell lines. Moreover, cells treated with citrate-modified Eu:HAp NPs exhibit stronger red luminescence in confocal images and enhanced cellular uptake in FACS analysis compared to those treated with bare Eu:HAp NPs. Therefore, due to their excellent biocompatibility and cellular uptake, the synthesized NPs are best suited for bioimaging applications. Furthermore, this approach can also be applied for surface modification with various targeting ligands for diverse applications.