Monodisperse Water-Stable Sio2-Coated Fluoride Upconversion Nanoparticles with Tunable Shell Thickness

Citation: Saleh TA (2016) Surface Enhanced Raman Scattering Spectroscopy for Pharmaceutical Determination. Int J Nanomater Nanotechnol Nanomed 2(1): 029-018. DOI: 10.17352/2455-3492.000012 Ji T, Xu X, Wang X, Zhou Q, Chen G (2017) Monodisperse Wa er-Stable Sio2-Coated Fluoride Upco version Nanoparticles with Tunable Shell Thickness. Int J Nanomater Nanotechnol Nanomed 3(1): 015-018. DOI: http://doi.org/10.17352/2455-3492.000015 Abstract


Introduction
In recent years, with the deepened understanding of the luminescence mechanism of lanthanide-doped upconversion nanoparticles (UCNPs) and the maturity of their synthesis methods, those new luminescent nanomaterials have spurred wide interests on many applications ranging from biomarker detection to biomedical imaging [1][2][3][4][5][6][7][8][9][10]. UCNPs have many excellent physical and chemical properties, such as infrared light excitation, strong penetrability of tissue, little damage to biological tissue, zero background fl uorescence, long fl uorescence lifetime, narrow emission band, and wide anti-Stokes shift and so on. However, the as-prepared UCNPs are typically hydrophobic (water-insoluble) and unable to link with bio-targeting biomolecules, restricting their applications in biology. For example, the solvo (hydro) thermal method and thermal decomposition method are commonly used approaches for synthesizing monodisperse UCNPs with good reproducibility [11][12][13][14]. Yet, the long-chain oleic acid capped on the surface prevent their further uses in biological environment. To solve this problem, the surface chemistry of as-prepared UCNPs have to be designed to grant both a stable aqueous colloidal dispersion and the ability to conjugate biomolecules. Several approaches has been attempted toward this regard, including SiO 2 coating, wrapping by small molecular surfactant, amphiphilic polymer, oxidizing oleic acid ligands with the Lemieuxvon Rudolf reagent, and ligand exchange [11,[15][16][17][18][19][20][21][22][23][24][25]. In particular, SiO 2 -coating are of particular interest, due to its high biocompatibility, easy surface modifi cation through silicon-enriched chemistry, and easy control of interparticle interactions [26][27][28][29]. However, there lacks a facile way to perform silica coating of UCNPs with a controlled thickness.
Herein, we used a high temperature co-precipitation method to synthesize hexagonal NaYF 4 : Yb, Er, Tm UCNPs capped by the oleic acid group. These UCNPs were then coated with a silica shell of different thickness via a modifi ed reverse microemulsion. Moreover, we found that all these silica-coated UCNPs are stable at pH = 7 biological physiological saline (the sodium chloride NaCl solution).

Materials and characterization
Rare-earth oxides, including yttrium chloride (YCl 3  Aladdin (Shanghai, China). Other reagents (analytical grade) were also purchased from Aladdin (Shanghai, China). All reagents were used as received without further purifi cation. Deionized water was used in all experiments. TEM images were performed on a JEM 2000FX (Jeol Ltd, Japan). Fluorescence spectra were recorded on Ocean optics spectrometers equipped with a near-infrared (NIR) laser with emission at 980 nm.

Synthesis of NaYF 4 : Yb,Er,Tm upconversion nanoparticles
The NaYF 4 : 20% Yb, 2% Er, 0.5% Tm nanocrystals were prepared using a high temperature co-precipitation method. First, the lanthanide chlorides containing 0.775 mmol YCl 3 .6H 2 O, 0.20 mmol YbCl 3 .6H 2 O, 0.02 mmol ErCl 3 .6H 2 O, 0.005 mmol TmCl 3. 6H 2 O were loaded to a 250 mL 3-necked fl ask, followed by adding 15 mL of octadecene and 9 mL of oleic acid. The fl ask was then heated to 150 under Ar for 30 min. Subsequently, the fl ask was cooled down to 50 and 10 mL methanol solution containing 0.1482 g NH 4 F and 0.1 g NaOH was added drop wise. The mixed solution was stirred at 50 for 2 h and heated slowly to 80 to remove methanol. The fl ask was heated up rapidly to 300 for 1 h, and then naturally cooled down to room temperature. The reaction solution was evenly divided into two 50 mL tubes, followed by adding 20 mL ethanol in each tube for centrifugation (6000 rpm, 5 min). After washing with ethanol for three more times, oleate-capped upconverting nanoparticles were stored in 10 mL cyclohexane for silica coating.

Synthesis of silica-coated NaYF 4 : Yb,Er,Tm upconversion nanoparticles with tunable shell thickness
The coating of upconversion nanoparticles with silica was achieved by a modifi ed reverse micro-emulsion method. Cyclohexane-dispersed UCNPs (20 mg/mL) with various amount of volume (1, 0.5, or 0.2 mL) were diluted by adding pure cyclohexane solvent to 2 mL, and then got transferred to a 60 mL glass bottle. After that, 8 mL of cyclohexane and 0.5 mL of Triton X-100 were added into the bottle along with about 2 min ultrasonication. Subsequently, 0.5 mL of Trit on X-100 and 0.12 mL of ammonium hydroxide (25-28 wt%) was added into the mixture under ultrasonication for about 20 min, yielding a transparent solution. Then, 40 L of TEOS were added and the mixture was ultrasonicated for 2 min, followed by magnetic stirring at room temperature for 48 h. The silica-coated NaYF 4 :Yb,Er, Tm UCNPs were collected by centrifugation, washed with ethanol three times, and fi nally dispersed in diff erent NaCl concentration of aqueous solution at different pH values.

Results and Discussion
Characterization of NaYF 4 : Yb,Er,Tm and NaYF 4 : Yb,Er,Tm@SiO 2 nanoparticles UCNPs (Y:Yb:Er:Tm=77.5:20:2:0.5) were synthesized by using a previously reported method with modifi cations [27]. The TEM image shows that the as-prepared nanoparticles have uniform size and morphology of hexagonal shape ( Figure   1). The average diameter of these particles was about 40 nm, suitable for biological applications. The surface of these UCNPs was capped by oleic acid, making them hydrophobic and preventing them from biological applications. To address this problem, we coated these UCNPs with a shell layer of silica that makes the core-shell water soluble. The silica coating strategy    Figure 4). The nanoparticles in the pH = 7 solution was the most stable, forming clear solution without precipitation over 5 h. While the nanoparticle solution was most unstable at pH = 3 solution, the precipitation could be observed after about 1 min. For weak acid or alkaline solution, the stability of the specifi c nanoparticles was superior to that at pH=3, but inferior than at pH=7. The combined results in Figure  3 and Figure 4 indicated that the silica-coating make UCNPs stable at neutral aqueous environment free of electrolyte. For the electrolyte-containing biological environments, further surface modifi cation of silica coating was needed such as polyethylene glycol (PEG) to improve blood-circulation capability.

Conclusion
We report on a modifi ed reverse microemulsion approach to yield uniform silica coating of NaYF 4 : Yb, Er, Tm UCNPs with a controlled thickness (3-16 nm). A simple increase of the concentration of UCNPs while maintaining the TEOS concentration constant could gradually decrease the silica shell thickness. Moreover, stability investigations revealed that the silica-coated UCNPs are most stable at sodium chloride-free solution and with pH=7. The stable, monodisperse, and uniform silica-coated UCNPs in aqueous solution have implications for applications in bioimaging.