Surface-Engineered Design of Efficient Luminescent Europium(III) Complex-Based Hydroxyapatite Nanocrystals for Rapid HeLa Cancer Cell Imaging.

We synthesized hydroxyapatite nanocrystals under the existence of tris(2,2,6,6-tetramethyl-3,5-heptanedionato)europium(III) (EuTH) complex to form inorganic/organic hybrid nanocrystal (EHA). Then, the folic acid derivative (folate N-hydroxysuccinimidyl ester (FA-NHS)) as the targeting ligand for the HeLa cancer cells was immobilized on the EHA by the mediation of both 3-aminopropyltriethoxysilane and methyltriethoxysilane molecules. Here, we investigated the photofunctions based on the interfacial interactions between the FA-NHS and EHA nanohybrids for preparing the novel bioimaging nanomaterials. As a result, the photofunctions could be changed by the FA-NHS molecular occupancy on the EHA. When the molecular occupancy ratio to the EHA surfaces is at around 3-5%, the intense luminescence from the f-f transition of the Eu3+ ions as well as the charge transfer between the EuTH-FA-NHS was observed to exhibit higher quantum efficiency. Moreover, effective dispersibility in phosphate-buffered saline was confirmed with immobilizing the positively charged FA-NHS. The cytotoxicity against the HeLa cells was also evaluated to verify whether the nanohybrids can be the candidate for cell imaging. The affinity and noncytotoxicity between the FA-NHS-immobilized EHA nanohybrids and cells were monitored for 3 days. Red luminescence from the cells could be observed, and the labels with following the cellular shapes were achieved by an additional culture time of 1 h after injecting the FA-NHS-immobilized EHA nanohybrids to the spheres, indicating the rapid bioimaging process. Therefore, this is the first successful report to describe the synthesis of inorganic-organic nanohybrid systems for controlling the EuTH-FA-NHS interactions. The photofunction of the interfacial interactions was successfully designed to provide "efficient luminescent ability" as well as "rapid targeting to the cancer cells" in one particle.