Prepration Of Rare Earth Elements Co-doped Hydroxyapatite Nanocrystals And Its Application In Bioimaging

Early detection of tumor malignancy is the crucial element for efficient treatment of cancer.Nano materials with properties of fluorescence,radioactivity and magnetism are helpful for labeling and early diagnose of cancer cells.The fluorescent imaging technology which is based on the luminescent materials is convenient for location of tumor and can improve the clearance of surgery.Hydroxyapatite?HAP?can be used as rare earth luminescence host materials based on its unique crystal structure.Furthermore,nano HAP shows good biodegradation in acid environment of cells.Therefore,rare earths doped HAP is promising to be a kind of biocompatible and biodegradable fluorescent imaging contrast agent.Current researching is focus on the improvement of fluorescent intensity to obtain higher imaging sensitivity.Calcination at high temperature and increase rare earth contents can improve luminescent intensity,but overlarge particle size and cytotoxicity will be induced.To avoid those problems,the study on rare earths?REs?co-doped HAP nano crystals?HAP:REs?with luminescence enhanced based on the energy transfer mechanism among rare earths was carried out in this paper.?1?Based on co-precipitation,the effect of co-doping group and molar ratios of REs as well as calcination on the luminescent properties of HAP:REs were studied.Results showed that among groups of Eu/Tm,Eu/Tb and Eu/Gd,Eu/Gd co-doping has the best luminescent enhancement efficiency.The crystal composition of products were not changed by REs co-doping,and the obtained HAP:Eu/Gd were plate-like crystals?9-13×30-60 nm?in plain size.For HAP:Eu/Gd synthesized at 80 ^oC,when Eu/Gd is 2:1.5,HAP:Eu/Gd has the best luminescent enhancement effect,and comparing to Eu single doped HAP samples?HAP:Eu?the luminescent intensity is improved about 150%?excited at 394 nm?.After calcined under 600 ^oC,the luminescent intensity increased sharply,and when Eu/Gd is 2:0.5,HAP:Eu/Gd shows best luminescent enhancement effect,the luminescent intensity is improved about60%compared to HAP:Eu,but calcination leaded to the crystals aggregation and overlarge particles size.For the luminescence enhancement mechanism of Eu/Gd co-doping,when excitated at 273 nm,it is mainly induced by energy transfer from ⁶P_J(Gd³⁺)to ⁵H_J(Eu³⁺);at 394 nm,it is attributed by the combination of Cooperation Upconversion and Successive Energy Transfer process between Eu and Gd.?2?Based on the optimized Eu/Gd molar ratio of HAP:Eu/Gd prepared by co-precipitation,the properties of HAP:Eu/Gd prepared by sol-gel were studied.At low temperatures of 400-600 ^oC,HAP:Eu/Gd nano crystals can be obtained.When excited at 350 nm,the main emission peak was observed at 575 nm and the intensity was similar to the products obtained by precipitation and calcined under 600 ^oC?excited at 394 nm and emission peak at 616 nm?.In this preparation method,the processs of REs diffused to Ca?II?site was accelerated by the existed redox reacton,and REs elements were mainly at the inversion centres.Compared to precipitation,particles aggregation and overlarge size are also appeared,but elements ratios of products can be accurately controlled by this metod.?3?For HAP:Eu/Gd nanocrystals obtained at 80 ^oC,biosafety,biodegradation and fluorescence imaging in vitro and in vivo were fully evaluated.Results demonstrated that HAP:Eu/Gd nanoparticles didn't cause hemolysis and showed no cytotoxicity to L02 cells.The accumulative degradation rate in HepG2 cells were about 60%.After co-cultured for 4h with HepG2 cells,HAP:Eu/Gd could be easily uptaken and achieved bioimaging in cells.Animal experiments in vivo?intraperitoneal and tail vein injection?showed that HAP:Eu/Gd can be used for bioimaging in tissues.However,HAP:Eu/Gd were cleared by RES and mainly accumulated in organs such as liver,spleen et al,so the surface of HAP:Eu/Gd nano crystals should be modified to reduce the clearance rate by RES in further researching works.