Shape-controllable synthesis of hydrophilic NaLuF4:Yb,Er nanocrystals by a surfactant-assistant two-phase system
© Zhou et al.; licensee Springer. 2013
Received: 16 October 2013
Accepted: 26 November 2013
Published: 6 December 2013
Water-soluble upconversion nanoparticles (UCNPs) were prepared by a one-pot procedure in a two-phase reacting system. Four kinds of surfactants were tested in the synthesis process as capping agent to tune size and morphology of nanocrystals. Nanoparticles (approximately 70 nm) and rods (400 nm and 2.5 μm) were synthesized, respectively. Then, Fourier transform infrared spectroscopy analysis confirmed the successful linking between UCNP surface and surfactant. Ionic liquids (ILs) and surfactants participated in synthesis process together, competing with each other to cap on UCNPs. ILs still led the competition of capping, while surfactants worked as cooperative assistants to develop functional surface. Further characterizations such as high-resolution transmission electron microscopy and X-ray diffraction indicated the changes in crystallization and phase transformation under the influence of surfactants. In addition, the growth mechanism of nanocrystals and upconversion fluorescence luminance was also investigated in detail. At last, the cytotoxicity of UCNPs was evaluated, which highly suggest that these surface-functionalized UCNPs are promising candidates for biomedical engineering.
KeywordsUpconversion Rare earths Surfactant Capping agent Luminescence Cytotoxicity
In the past decades, lanthanide (Ln)-doped upconversion nanoparticles (UCNPs) have attracted considerable attentions in the area of solar cells, detection of heavy metal in effluent and biomedical engineering including molecular imaging, targeted therapy and diagnosis all over the world due to their distinctive chemical and optical properties [1–4]. The unnatural UC behavior, converting near-infrared radiation (typically 980 nm) to high-energy emissions, has many unique advantages in biology field, including auto-fluorescence minimization, large anti-stokes shifts and penetrating depth, narrow emission peaks, and none-blinking [1, 2, 5]. However, conventional downconversion (DC) emission, such as quantum dots (QDs), has some intrinsic limitations including inherent toxicity and chemical instability in the bio-system despite of their tunable size-dependent emission and high quantum yields [6, 7].
The choice of the host material is a key factor for achieving efficient UC luminescence. Among all of the studied UC host materials such as oxides, fluorides, and vanadates, Ln-doped fluorides (NaLnF4) are considered to be the most efficient host matrices for UC emission due to its low phonon energy, which decreases the non-radiative relaxation probability and results in more efficient UC emissions . Especially, a lot of research has focused on the study of NaYF4[7–12]. Recently, reports on NaLuF4 have become increasingly impressive and showed its brighter potential. For example, Li’s group have resoundingly synthesized sub-20 nm  and sub-10 nm  water-stable Lu-UCNPs, which can be an ideal choice for multimodal imaging (UCL/CT/MRI/PET) agents. Notably, the sub-20 nm NaLuF4 co-doped Yb3+and Er3+(Tm3+) show about tenfold stronger UCL emission than that of corresponding hexagonal NaYF4-based nanocrystals with a 20-nm diameter, forecasting NaLuF4 an ideal host for multimodal bio-imaging probes [14, 15].
Up to date, great efforts have been devoted to the synthesis of high-quality UCNPs typically through hydrothermal reaction and thermal decomposition of RE organic precursors, two most commonly used synthetic methods. However, they still have their respective defects albeit successful in some respects. For instance, typical synthetic methods generally need complicated post surface modification to couple with functional groups for hydrophily and biocompatibility , which is a two-step synthesis. Recently, our group has introduced a novel oleic acid-ionic liquids (OA-ILs) dual phase synthesis method, by which hydrophilic and hydrophobic Ln-doped upconversion crystals could be selectively synthetized in a one-pot approach [17–19]. In fact, the hydrophilic products obtained by dual-phase method are poorly dispersed and easy to get aggregated in solution because of the complicated surface groups coming from ILs. In a word, one-step synthesis method can simplify the reaction procedure, while products by the two-step synthesis can have better uniformity and monodispersity. As we know that some hydrophilic agents can participate in ligand exchange reaction to endow nanomaterial with hydrophilia and good monodispersity, including sodium citrate , polyethylene glycol (PEG) , EDTA [22, 23], 6-aminohexanoic acid (AA) , etc.
Herein, we introduced a representative surfactants into OA-ILs two-phase reaction system to improve the dispersity, by using the notion of OA-ILs two-phase approach (the advantage of one-pot strategy) and ligand exchange functionalization (the advantage of better dispersity). Sodium dodecyl sulfate (SDS) and dodecyl dimethyl benzyl ammonium chloride (DDBAC) represent anionic and cationic surfactants, while PEG and sodium citrate (Cit-Na) present non-ionic surfactants with hydroxyl and carboxyl, respectively. Cit-Na is regarded as a good chelating agent in order to prevent further aggregation of particles . SDS has a comparatively high HLB (up to 40) , which means that it is able to provide considerable anionic hydrophilic groups. DDBAC, the positively charged quaternary ammonium salt can make itself absorbed on the surface with negative charge . PEG is a polymer comes from polyhydric alcohols with relatively large viscosity. Various active groups of surfactants successfully capped onto nanocrystals surface during the synthetic process, resulting in Cit-UCNPs, SDS-UCNPs, DDBAC-UCNPs, and PEG-UCNPs. The size, morphology, phase, and emission intensity of the above four UCNPs were also investigated compared to those without surfactants (IL-UCNPs).
All RE oxides, including Lu2O3 (99.99%), Yb2O3 (99.99%), and Er2O3 (99.99%), were obtained from Aladdin Chemistry, Shanghai, China. Sodium oleate, OA, ethanol, Cit-Na, PEG, DDBAC, and SDS were purchased from Sinopharm Chemical Reagent, Shanghai, China. BmimPF6 was purchased from Shanghai Cheng Jie Chemical, Shanghai, China. MGC-803cells and GES-1 cells were available from the cell store of the Chinese Academy of Science, Shanghai, China. Cell culture products and reagents, unless mentioned otherwise, were purchased from GIBCO, Langley, OK, USA. Deionized water (Millipore Milli-Q grade, Billerica, MA, USA) with a resistivity of 18.2 MW cm was used throughout the synthetic and post-synthetic treatment procedures.
Synthesis of NaLuF4:Yb, Er with different surfactants
RE-(oleate)3 complexes (RE = Lu, Yb, Er) were synthesized according to previously reported methods [15, 27]. Typically, 0.78 mmol Lu(oleate)3), 0.2 mmol Yb(oleate)3, 0.02 mmol Er(oleate)3, and 1 mmol sodium oleate were dissolved in a small amount of OA at elevated temperature under vigorous magnetic stirring to form a homogeneous solution. Then, the solution was transferred into a 50-mL Teflon-lined autoclave, which contained 15 ml BmimPF6 to form a two-phase reaction system. Finally, 10 mL ethanol solutions including 0.1 mmol surfactants (Cit-Na, PEG, DDBAC, SDS) were added and the two-phase system was heated to 250°C and maintained for 24 h. The whole system was allowed to cool to room temperature. All precipitates were found in the IL phase. The particles were isolated by means of centrifugation at a speed of 8,500 rpm. The products were washed with ethanol under ultrasonic conditions for several times to remove the residue. Finally, the products were dried at 70°C under vacuum overnight.
The morphology of the nanocrystals was determined by scanning electron microscopy (FEI-Sirion 200, Hillsboro, OR, USA) and transmission electron microscopy (JEM 2100 F, JEOL Ltd., Akishima-shi, Japan). Powder X-ray diffraction (XRD) measurements were conducted on a X-ray diffractometer (Rigaku, Shibuya-ku, Japan) with Cu Kα radiation at 1.540 Å at a scanning rate of 4° min-1 in the 2θ range from 10° to 70°. Fourier transform infrared spectroscopy (FTIR) analysis was carried out on an EQUINOX 55 spectrometer (Bruker, Karlsruhe, Germany). UC fluorescence spectra were characterized using a Fluorolog-3 spectrofluorometer (JobinYvon, Palaiseau, France) at room temperature. Thermogravimetric analysis (TGA) analyses were carried out on a Pyris 1 TGA instrument (PerkinElmer, Waltham, MA, USA).
Cell culture and cytotoxicity assay
Human gastric cancer MGC-803 cells and human normal gastric GES-1 cells were grown in RPMI-1640 medium with 10% fetal bovine serum (FBS) and 1% penicillin at 37°C in a humidified 5% CO2atmosphere. MGC-803 cells and GES-1 cells (4 × 103 cells/well) were seeded in 96-well plates and incubated overnight. After being rinsed with PBS, the cells were incubated with varying concentrations of Cit-Na modified NaLuF4:Yb, Er UCNPs (0, 5, 10, 20,40, 80 μg/mL) prepared above for 12 h at 37°C in the dark under the same conditions. Cell viability was determined by methyl thiazolyl tetrazolium (MTT) assays. MTT (20 μL, 5 mg/mL) was added to each well, and then, the plate was incubated for another 4 h. The medium was removed, and the formazan crystals formed were dissolved in 150 μL of dimethylsulfoxide (DMSO). The absorbance at 570 nm was measured with a standard microplate reader (Scientific Multiskan MK3, Thermo, Waltham, MA, USA). Results were calculated as percentages relative to control cells. Data are mean ± standard deviation from three independent experiments.
Results and discussion
To evaluate the ligand stability in each sample, TGA was performed (Additional file 1: Figures S1c, S2c, S3c, S4c, S5c). TGA curves showed two weight loss stages in the range of 20°C to 900°C. The first weight loss stage in the temperature range of 20°C to 200°C was due to the loss of absorbed water. The second stage from 200°C to 900°C was attributed to the combustion of the organic groups in the samples. A common feature was that weight of each sample decreased rapidly at 600°C to 700°C. Additionally, when temperature reached 600°C, the weight loss was still less than 10% of the total weight, indicating good stability of each ligand linking. Notably, Cit-Na had shown priority in chelate ability, whose weight loss was only 1.82% until temperature risen up to 900°C. Based on EDX spectrums (Additional file 1: Figures S1d, S2d, S3d, S4d, S5d), fluorine had occupied majority weight of UCNPs, demonstrating that the lead role of capping agent was still ILs, and other surfactants worked as cooperative assistants to develop functional surface.
In summary, water-soluble NaLuF4:Yb,Er nanocrystals were synthesized via a simple IL-assisted dual-phase method. Surfactants were added into reaction system as capping agents to endow UCNPs with functional groups in one-step synthesis. According to SEM and TEM images, the presence of surfactants could regulate size and morphology of nanocrystals from 20- to 30-nm nanoparticles to microrods with diverse sizes. What is more, the dispersity of UCNPs was improved, accompanied with narrower particle size distribution. The FTIR analysis confirmed that the active groups had been successfully attached into the surface of UCNPs even though they had to compete with ILs. Then XRD analysis revealed that Cit-UCNPs were co-existing α and β phase, while SDS, DDBAC, and PEG functional nanocrystals have transformed into microrods with pure β phase, indicating the achievement of simultaneous phase and shape control in one step. Moreover, under the excitation of a 980-nm laser diode, visible green light emissions were observed in both solution and powder. Based on the UCL spectra, the emission intensity increased dramatically after adding surfactants. Finally, cytotoxicity of Cit-NaLuF4:Yb,Er was evaluated, showing prepared UC nanocrystals own good biocompatibility, indicating its potential applications in biomedical engineering in near future. Further work will focus on application of prepared NaLuF4:Yb,Er nanoparticles in bio-imaging, such as fluorescent imaging of cancer cells and targeted therapy in vivo.
This work is supported by the National Key Basic Research Program (973 Project) (no. 2010CB933901 and 2011CB933100), National Natural Scientific Fund (no. 81225010, 81327002, and 31100717), 863 project of China (2012AA022703), Shanghai Science and Technology Fund (No.13NM1401500), Shanghai Jiao Tong University Innovation Fund for Postgraduates (no. AE340011).
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