SURFACE MODIFICATION OF NaYF4:Yb,Er UPCONVERSION NANOPARTICLES FOR BIOAPPLICATION QIAN LIPENG (B. Eng., TIANJIN UNIVERSITY) (M. Eng., TIANJIN UNIVERSITY) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF MATERIALS SCIENCE AND ENGINEERING NATIONAL UNIVERSITY OF SINGAPORE 2012 Acknowledgements I would like to express my deepest gratitude to my supervisor, Professor Chow Gan-Moog, for his patient guidance and warm encouragement that made this thesis possible. I benefit from his expertise in many aspects of scientific research. I would like to express my sincere appreciation to Associate Professor Too Heng-Phon, who guided me on the section of bio-application part. His knowledge and experience in biochemistry are impressive. I would like to acknowledge the assistance of Mr. Zhou Lihan with the cell work. I would also like to express my thanks for the encouragement and suggestions from group members, Dr. Yi Guangshun, Mr Yuan Du and Mr Karvianto. I also thank the administrative and technical support from Department of Material Science and Engineering at NUS. i Table of Contents Acknowledgements . i Table of Contents .ii Summary .vii List of Tables . ix List of Figures . x Chapter Introduction . 1.1 Background . 1.2 Upconversion materials 1.2.1 Upconversion process 1.2.2 Selection of Suitable Dopants and Host . 1.3 Synthesis of UC nanoparticles 1.4 Surface modification of UC nanoparticles 1.4.1 Surface passivation . 1.5 1.4.2 Silica coating 10 1.4.3 PEGylated silica shell coated UC nanoparticles 12 UC nanoparticles for bio-applications 13 1.5.1 In vitro cell imaging . 15 1.5.2 Photothermal therapy for cancer cell 17 ii 1.6 Objective . 19 1.7 Outline of the thesis 21 Chapter Characterization techniques 22 2.1 X-ray Diffraction (XRD) 22 2.2 Transmission Electron Microscopy (TEM) 22 2.3 Photoelectron Spectroscopy 23 2.3.1 Ultraviolet Photoelectron Spectroscopy (UPS) 24 2.3.2 X-ray Photoelectron Spectroscopy (XPS) 24 2.4 Optical characterization 25 2.4.1 Fourier transform infrared spectroscopy (FTIR) 25 2.4.2 Raman spectroscopy . 25 2.4.3 UV-vis absorption spectroscopy 25 2.4.4 Luminescence spectrometer . 26 2.5 Inductively coupled plasma analysis (ICP) 26 2.6 Thermogravimetry Analysis (TGA) . 27 2.7 Measurement of Zeta potential . 27 2.8 Dynamic light scattering (DLS) 28 Chapter Synthesis and characterization of UC nanoparticles . 30 3.1 Experimental method 30 3.2 NaYF4:Yb,Er UC nanoparticles 32 iii 3.3 3.2.1 Characterization . 32 3.2.2 Energy structure . 35 NaYF4:Yb,Er / NaYF4 (core/shell) nanoparticles . 39 3.3.1 Characterization . 39 3.3.2 UC luminescence properties . 41 3.3.3 Shell thickness effect 45 3.4 Core/shell structure of UC Nanoparticles . 46 3.5 Dopant diffusion in core/shell structure 50 3.6 Summary . 57 Chapter Synthesis of silica coated UC nanoparticles 59 4.1 Experimental method 59 4.2 Silica coated UC nanoparticles . 61 4.2.1 Characterization . 61 4.2.2 Mechanism of reverse micro-emulsion 62 4.2.3 Energy band gap of silica shell 64 4.3 Amino functionalized silica coated UC nanoparticles 66 4.4 PEGylation of silica coated UC nanoparticles 69 4.5 Comparison of undoped NaYF4 and silica shell . 76 4.6 NaYF4:Yb,Er / NaYF4 / silica (core/shell/shell) nanoparticles . 78 4.7 Summary . 79 iv Chapter Gold decorated UC/shell/silica nanocomposites . 81 5.1 Experimental method 81 5.2 Synthesis of UC/shell/Au-silica nanocomposites . 82 5.2.1 Characterization . 82 5.2.2 Mechanism of reverse micro-emulsion 84 5.3 UC properties of UC/shell/Au-silica nanocomposites 88 5.4 Dependence of UC emission on gold concentration . 90 5.5 Calculated extinction properties of UC/shell/Au-silica 93 5.5.1 Simulation of single Au nanoparticles . 94 5.5.2 Simulation of silica and Au shell nanoparticles . 95 5.5.3 Simulation of UC/shell/Au-silica . 96 5.5.4 The effect of Au concentration on extinction spectra of UC/shell/Au-silica 98 5.6 Summary . 100 Chapter Bio-application 102 6.1 Experimental method 102 6.2 Behavior of nanoparticles in bio media 104 6.3 6.2.1 Bio media . 104 6.2.2 Emission intensity of nanoparticles 106 6.2.3 Stability of nanoparticles 108 Cell imaging 112 v 6.4 6.5 Photothermal therapy 113 6.4.1 Photothermal measurement 114 6.4.2 Photothermal destruction of neuroblastoma cells in vitro 117 6.4.3 Time effect of photothermal destruction of cancer cell . 121 Summary . 123 Chapter Conclusions and recommendations . 124 7.1 Conclusions . 124 7.2 Recommendations for future work . 126 Bibliography . 127 Appendix . 147 A. Calculation of reaction yield of NaYF4:Yb,Er nanoparticles . 147 B. Calculation of the average distance between two nearest Er ions in NaYF4:xEr nanoparticles 148 C. Calculation of the thickness of the Er and Yb co-doped interface of Er/Yb (core/shell) nanoparticles . 149 vi Summary Motivated by using NaYF4:Yb,Er upconversion nanoparticles as potential bioprobe for cell imaging and thermal therapy, this thesis studies the surface modification of these NaYF4:Yb,Er nanoparticles by undoped NaYF4 shell, amorphous silica and Au nanoparticles. NaYF4:Yb,Er nanoparticles with a particle size of 11.1 ± 1.3 nm were synthesized by a thermal decomposition method. The NaYF4:Yb,Er / NaYF4 (core/shell) nanoparticles obtained by the same synthesis method showed that an undoped NaYF4 shell significantly enhanced the emission intensity by 15 times, and the critical shell thickness was ∼3 nm. The diffusion of Yb and Er dopants in core/shell structure and the energy transfer distance between Yb and Er were also studied. Amorphous silica shells, commonly used for functionalization of inorganic nanoparticles in bio-applications, were coated on NaYF4:Yb,Er nanoparticles via a reverse micro-emulsion method using dual surfactants of polyoxyethylene (5) nonylphenylether and 1-hexanol, and tetraethyl orthosilicate as precursor. The thickness of silica shell was ~ nm. The emission intensities of silica coated NaYF4:Yb,Er nanoparticles remained the same as that of uncoated nanoparticles after surface functionalization with an amino group using (3-aminopropyl)-trimethoxysilan and PEG using mPEG-silane. Silica, though providing a good barrier to the nonradiative relaxation between the upconversion nanoparticles and the environments, did not enhance the emission intensity of upconversion nanoparticles. Gold decorated NaYF4:Yb,Er / NaYF4 / silica (core/shell/shell) upconversion nanocomposites (∼70-80 nm) were further synthesized using chloroauric acid in a vii one-step reverse micro-emulsion method. Gold nanoparticles (~ nm) were deposited on the surface of silica shell of these core/shell/shell nanocomposites. The total upconversion emission intensity (green, red and blue) of the core/shell/shell nanocomposites decreased by ~ 52% after Au was deposited on the surface of silica shell. Both the experimental results and the simulation study confirmed that the decrease in total emission intensity was due to the scattering effect of Au nanoparticles. The upconverted green light of the UC nanoparticles was coupled with the surface plasmon of Au leading to rapid heat conversion. Gold decorated NaYF4:Yb,Er / NaYF4 / silica (core/shell/shell) upconversion nanocomposites demonstrated strong photothermal effect and cancer cells destruction efficiency. 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Gulik, Lesion progression with time and the effect of 145 vascular occlusion following radiofrequency ablation of the liver. Br. J. Surg., 2003. 90 (3): 306-312. 146 Appendix A. Calculation of reaction yield of NaYF4:Yb,Er nanoparticles In NaYF4:20%Yb,2%Er precursor, the concentrations of Y, Yb and Er are as follows. Y 0.2 M ×11.7 mL /12 mL = 0.195 M Yb 0.2 M ×3 mL /12 mL = 0.05 M Er 0.2 M ×0.3 mL /12 mL = 0.005 M In each reaction, 0.5 mL precursor was used. Assuming it is a complete reaction, the weight of the final product should be as follows. Mole weight of final NaYF4:20%Yb,2%Er product: 0.195 M × 0.5 mL + 0.05 M × 0.5 mL + 0.005 M × 0.5 mL = 0.125 mmol Weight of final NaYF4:20%Yb,2%Er product: 0.125 mmol × 206.3 g/mol = 25.8 mg The final yield in this reaction: 19 mg / 25.8 mg = 74% 147 B. Calculation of the average distance between two nearest Er ions in NaYF4:xEr nanoparticles The volume of one hcp NaYF4 unite cell can be calculated as follows (Figure B). Figure B Structure of hcp NaYF4 crystal. Volume =c × a × a sin 60° = 3.53 × 5.96 × 5.96 × sin 60° = 108.6 Å3 Each unit cell contains 1.5 Y atoms. So the volume per Y atom occupied is equal to 108.6 / 1.5 = 72.4 Å3. From the doping concentration of Er, the volume of each Er ion occupied and also the average distance between two nearest Er ions can be calculated. For instance, the average distance of Er ions in NaYF4:2%Er was calculated as follows. The volume per Er atom occupied: 72.4 / 0.02 = 3620Å3. The average distance between two nearest Er ions: (3620 Å3)1/3 = 15.35 Å 148 C. Calculation of the thickness of the Er and Yb co-doped interface of Er/Yb (core/shell) nanoparticles For Er/Yb (core/shell) nanoparticles, R is the radius of the Er doped core and W is the thickness of the interface of core/shell nanoparticles (Figure C). Er/Yb (core/shell) Yb Er R R W Before Yb diffusion After Yb diffusion Figure C Schematic illustration of Er/Yb (core/shell) nanoparticle before and after Yb diffusion. The volume of Er doped core before and after Yb diffusion are ¾πR3 and ¾π(R-W)3, respectively. So the volume of Er and Yb co-doped interface can be represented as ¾πR3 - ¾π(R-W)3. For UC/shell nanoparticles, the volume of the UC core is ¾πR3. Based on the emission result, the thickness of the interface W can be calculated as follows. (¾πR3 - ¾π(R-W)3) / (¾πR3) = 0.124 ⇒ (R-W) R3 =1-0.124 Taking R = 11 nm (from section 3.2.1) into above equation, W = 0.25 nm 149 [...]... pattern of the NaYF4: Yb,Er / NaYF4 (core/shell) nanoparticles 39 Figure 3.8 TEM image and HRTEM image (inset) of the NaYF4: Yb,Er / NaYF4 (core/shell) nanoparticles 40 Figure 3.9 UC luminescence spectra of NaYF4: Yb,Er and NaYF4: Yb,Er / NaYF4 (core/shell) nanoparticles under 980nm NIR excitation UC luminescence image (inset) of NaYF4: Yb,Er and NaYF4: Yb,Er / NaYF4 (core/shell) nanoparticles. .. luminescence spectra of NaYF4 and NaYF4: Yb,Er nanoparticles under 980nm NIR excitation UC luminescence image (inset) of NaYF4: Yb,Er nanoparticles in hexane under 980 nm excitation 35 Figure 3.4 UPS spectra of undoped NaYF4, NaYF4: Yb and NaErF4 nanoparticles 37 Figure 3.5 UV-vis absorption of NaYF4 and NaYF4: Yb,Er nanoparticles in hexane 38 Figure 3.6 Energy level diagram of NaYF4: Yb,Er nanoparticles. .. factor of ~10, compared to the same bulk materials.11 Another study showed that a quantum yield of 0.005% was measured for 10 nm NaYF4: Yb,Er nanoparticles while the quantum yield of 3% was measured for a bulk sample.24 The mechanism of size-dependent UC properties may be attributed to the surface ligands quenching, surface defects and surface segregation.25 Therefore, surface modification of UC nanoparticles. .. coating on UC nanoparticles by a reverse microemulsion method to convert hydrophobic UC nanoparticles to hydrophilic, and further surface modification of silica shell by PEG and amino group 4 Use of Au nanoparticles to further decorate the surface of silica coated UC nanoparticles by a reverse micro-emulsion and study of the effect of concentration of Au nanoparticles on the emission of UC nanoparticles. .. image of the UC/silica nanoparticles 61 Figure 4.2 Emission spectra of NaYF4: Yb,Er, UC/silica and silica nanoparticles 62 Figure 4.3 A schematic diagram of deposition of silica coating on hydrophobic NaYF4: Yb,Er nanoparticles by a reverse micro-emulsion method Stage (a): oleylamine coated NaYF4: Yb,Er nanoparticles, NP-5 and 1-hexanol dispersed in cyclohexane Stage (b): micro-emulsion formed... with Au nanoparticles to generate heat for thermal therapy The objectives of this thesis include: 1 Synthesis of 11 nm NaYF4: Yb,Er UC nanoparticles by pyrolysis and study of their emission property and energy band structure 2 Use of undoped NaYF4 shell to enhance the emission intensity of UC nanoparticles and study of the distance and distribution of dopants in coreshell structure 3 Deposition of a thin... previous work.11, 20 1.4 Surface modification of UC nanoparticles Near infrared (NIR)-to-visible Ln doped UC nanoparticles have attracted significant interests due to potential applications as sensitive bio- probes To date, most of the works on UC nanoparticles as bio- probe has focused on Yb and Er codoped NaYF4 (NaYF4: Yb,Er) due to its highest UC efficiency As a bio- probe, the size of targeted cell (several... of undoped NaYF4 shell and silica shell on the emission intensity of UC nanoparticles will be compared PEGylation and amino functionalization of silica shell will also be carried out and the stability of PEGylated and amino functionalized silica coated UC nanoparticles in bio media will be studied 1.5 UC nanoparticles for bio- applications UC nanoparticles are very promising as a luminescent probe for. .. effects of size, shape and surface modification of UC nanoparticles on toxicity deserve further detailed study As an example, silica is often used as a shell coating on UC nanoparticles for bio- application since silica is so-called biocompatible.87 However, asbestos as a nanosize silicate material is carcinogenic Other issues may need to be addressed before UC nanoparticles can be commercially applied For. .. (several to tens of nanometers) requires the bio- probes are nano-sized with a narrow size distribution.23 High emission efficiency of UC nanoparticles is also desirable in applications Unfortunately, the emission intensity of UC nanoparticles is significantly reduced compared to their bulk counterparts For example, a sharp decrease of emission intensity was reported for NaYF4: Yb,Er UC nanoparticles ( . 100 Chapter 6 Bio- application 102 6.1 Experimental method 102 6.2 Behavior of nanoparticles in bio media 104 6.2.1 Bio media 104 6.2.2 Emission intensity of nanoparticles 106 6.2.3 Stability of nanoparticles. SURFACE MODIFICATION OF NaYF 4 :Yb,Er UPCONVERSION NANOPARTICLES FOR BIO- APPLICATION QIAN LIPENG (B. Eng., TIANJIN. Upconversion process 2 1.2.2 Selection of Suitable Dopants and Host 3 1.3 Synthesis of UC nanoparticles 7 1.4 Surface modification of UC nanoparticles 8 1.4.1 Surface passivation 8 1.4.2 Silica coating