The biosafety of lanthanide upconversion nanomaterials.

Lanthanide upconversion nanophosphors (UCNPs) show unique upconversion luminescence where lower-energy photons (such as near-infrared (NIR) excitation) are converted into higher-energy photons covering the NIR to the UV region, and are considered to have a bright future in clinical translation. As UCNPs are used in a significant number of potential bio-applications, their biosafety is important and has attracted significant attention. In this critical review, recent reports regarding the cellular internalization, biodistribution, excretion, cytotoxicity and in vivo toxic effects of UCNPs are reviewed. In particular, the studies which evaluated the association between the chemical and physical properties of UCNPs and their biodistribution, excretion, and toxic effects are presented in detail. Finally, we also discuss the challenges of ensuring the biosafety of UCNPs in vivo.

[1]  P. Choyke,et al.  In vivo multiple color lymphatic imaging using upconverting nanocrystals , 2009 .

[2]  Xiaohong Sun,et al.  Fabrication of Ag@SiO(2)@Y(2)O(3):Er nanostructures for bioimaging: tuning of the upconversion fluorescence with silver nanoparticles. , 2010, Journal of the American Chemical Society.

[3]  Huimao Zhang,et al.  Conjugation of NaGdF4 upconverting nanoparticles on silica nanospheres as contrast agents for multi-modality imaging. , 2013, Biomaterials.

[4]  Wei Feng,et al.  Sub-10 nm hexagonal lanthanide-doped NaLuF4 upconversion nanocrystals for sensitive bioimaging in vivo. , 2011, Journal of the American Chemical Society.

[5]  Yang Yang,et al.  High-quality water-soluble and surface-functionalized upconversion nanocrystals as luminescent probes for bioimaging. , 2011, Biomaterials.

[6]  Guixia Liu,et al.  Functionalization of upconverted luminescent NaYF4:Yb/Er nanocrystals by folic acid–chitosan conjugates for targeted lung cancer cell imaging , 2011 .

[7]  P. Perriat,et al.  Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging. , 2007, Journal of the American Chemical Society.

[8]  Jie Shen,et al.  Stem Cell Labeling using Polyethylenimine Conjugated (α-NaYbF4:Tm3+)/CaF2 Upconversion Nanoparticles , 2013, Theranostics.

[9]  Hans H Gorris,et al.  Tuning the Dual Emission of Photon‐Upconverting Nanoparticles for Ratiometric Multiplexed Encoding , 2011, Advanced materials.

[10]  Yun Sun,et al.  Dual-modality in vivo imaging using rare-earth nanocrystals with near-infrared to near-infrared (NIR-to-NIR) upconversion luminescence and magnetic resonance properties. , 2010, Biomaterials.

[11]  Chun-Hua Yan,et al.  Bioimaging and toxicity assessments of near-infrared upconversion luminescent NaYF4:Yb,Tm nanocrystals. , 2011, Biomaterials.

[12]  Leyu Wang,et al.  Preparation and upconversion luminescence cell imaging of O-carboxymethyl chitosan-functionalized NaYF4:Yb3+/Tm3+/Er3+ nanoparticles , 2013 .

[13]  Zach DeVito,et al.  Opt , 2017 .

[14]  Yong Zhang,et al.  Nanoparticles in photodynamic therapy: an emerging paradigm. , 2008, Advanced drug delivery reviews.

[15]  Dongmei Wu,et al.  Core-shell NaYF4:Yb3+,Tm3+@FexOy nanocrystals for dual-modality T2-enhanced magnetic resonance and NIR-to-NIR upconversion luminescent imaging of small-animal lymphatic node. , 2011, Biomaterials.

[16]  Wei Feng,et al.  Upconversion nanoparticles dramatically promote plant growth without toxicity , 2012, Nano Research.

[17]  John-Christopher Boyer,et al.  Absolute quantum yield measurements of colloidal NaYF4: Er3+, Yb3+ upconverting nanoparticles. , 2010, Nanoscale.

[18]  Zhigang Chen,et al.  Facile Epoxidation Strategy for Producing Amphiphilic Up-Converting Rare-Earth Nanophosphors as Biological Labels , 2008 .

[19]  F. Auzel.  Upconversion and anti-Stokes processes with f and d ions in solids. , 2004, Chemical reviews.

[20]  Huan Xu,et al.  Towards whole-body imaging at the single cell level using ultra-sensitive stem cell labeling with oligo-arginine modified upconversion nanoparticles. , 2012, Biomaterials.

[21]  Francisco Sanz-Rodríguez,et al.  Bio-functionalization of ligand-free upconverting lanthanide doped nanoparticles for bio-imaging and cell targeting. , 2012, Nanoscale.

[22]  Yun Sun,et al.  Core-shell lanthanide upconversion nanophosphors as four-modal probes for tumor angiogenesis imaging. , 2013, ACS nano.

[23]  Prakash Chandra,et al.  Enhanced upconversion luminescence in NaGdF4:Yb,Er nanocrystals by Fe3+ doping and their application in bioimaging. , 2013, Nanoscale.

[24]  J. W. Ding,et al.  Enhancement of up-conversion luminescence in Zn2SiO4:Yb3+, Er3+ by co-doping with Li+ or Bi3+ , 2012, Applied Physics B.

[25]  Taeghwan Hyeon,et al.  Nonblinking and Nonbleaching Upconverting Nanoparticles as an Optical Imaging Nanoprobe and T1 Magnetic Resonance Imaging Contrast Agent , 2009 .

[26]  Wei Feng,et al.  Biodistribution of sub-10 nm PEG-modified radioactive/upconversion nanoparticles. , 2013, Biomaterials.

[27]  Xiaohan Liu,et al.  A "neck-formation" strategy for an antiquenching magnetic/upconversion fluorescent bimodal cancer probe. , 2010, Chemistry.

[28]  Gun Hyuk Jang,et al.  A systematic in-vivo toxicity evaluation of nanophosphor particles via zebrafish models. , 2014, Biomaterials.

[29]  Chun-Hua Yan,et al.  Paradigms and challenges for bioapplication of rare earth upconversion luminescent nanoparticles: small size and tunable emission/excitation spectra. , 2014, Accounts of chemical research.

[30]  X. Qian,et al.  Facile preparation of well-defined hydrophilic core-shell upconversion nanoparticles for selective cell membrane glycan labeling and cancer cell imaging. , 2014, Analytical chemistry.

[31]  Xueru Zhang,et al.  Effect of Li+ ions on enhancement of near-infrared upconversion emission in Y2O3:Tm3+/Yb3+ nanocrystals , 2012 .

[32]  Wei Feng,et al.  Cubic sub-20 nm NaLuF(4)-based upconversion nanophosphors for high-contrast bioimaging in different animal species. , 2012, Biomaterials.

[33]  B. Levine,et al.  Cell biology: Autophagy and cancer , 2007, Nature.

[34]  Fuyou Li,et al.  A versatile fabrication of upconversion nanophosphors with functional-surface tunable ligands , 2010 .

[35]  Liang Cheng,et al.  Protein modified upconversion nanoparticles for imaging-guided combined photothermal and photodynamic therapy. , 2014, Biomaterials.

[36]  Zhengquan Li,et al.  Tracking transplanted cells in live animal using upconversion fluorescent nanoparticles. , 2009, Biomaterials.

[37]  Qian Liu,et al.  18F-Labeled magnetic-upconversion nanophosphors via rare-Earth cation-assisted ligand assembly. , 2011, ACS nano.

[38]  Jun Lin,et al.  A facile fabrication of upconversion luminescent and mesoporous core-shell structured β-NaYF4:Yb3+, Er3+@mSiO2 nanocomposite spheres for anti-cancer drug delivery and cell imaging. , 2013, Biomaterials science.

[39]  V. Dravid,et al.  Multimodal bioimaging using rare earth doped Gd2O2S: Yb/Er phosphor with upconversion luminescence and magnetic resonance properties. , 2013, Journal of materials chemistry. A.

[40]  W. Cao,et al.  Enhancement of upconversion luminescence of Y 2O 3:Er 3+ nanocrystals by codoping Li +Zn 2+ , 2011 .

[41]  Zhiguo Zhang,et al.  Upconversion Emission Enhancement in Yb3+/Er3+-Codoped Y2O3 Nanocrystals by Tridoping with Li+ Ions , 2008 .

[42]  Yi Lu,et al.  An exceptionally simple strategy for DNA-functionalized up-conversion nanoparticles as biocompatible agents for nanoassembly, DNA delivery, and imaging. , 2013, Journal of the American Chemical Society.

[43]  Jung Ho Yoo,et al.  Facile Synthesis of Ultrasmall and Hexagonal NaGdF4: Yb3+, Er3+ Nanoparticles with Magnetic and Upconversion Imaging Properties , 2010 .

[44]  R. Roy,et al.  Carbohydrate-coated lanthanide-doped upconverting nanoparticles for lectin recognition , 2010 .

[45]  W. Cai,et al.  Enhanced upconversion emission in Yb3+ and Er3+ codoped NaGdF4 nanocrystals by introducing Li+ ions. , 2012, Nanoscale.

[46]  J. Lee,et al.  High enhancement of green upconversion luminescence of Li+/Er3+/Yb3+ tri-doped CaMoO4 , 2012 .

[47]  M. Tan,et al.  Surfactant effects on efficiency enhancement of infrared-to-visible upconversion emissions of NaYF4:Yb-Er. , 2011, ACS applied materials & interfaces.

[48]  Qian Liu,et al.  Multifunctional rare-earth self-assembled nanosystem for tri-modal upconversion luminescence /fluorescence /positron emission tomography imaging. , 2011, Biomaterials.

[49]  Wei Feng,et al.  Polyphosphoric acid capping radioactive/upconverting NaLuF4:Yb,Tm,153Sm nanoparticles for blood pool imaging in vivo. , 2013, Biomaterials.

[50]  Bingbo Zhang,et al.  Upconverting rare-earth nanoparticles with a paramagnetic lanthanide complex shell for upconversion fluorescent and magnetic resonance dual-modality imaging , 2013, Nanotechnology.

[51]  Jing Chen,et al.  Controllable synthesis of NaYF(4) : Yb,Er upconversion nanophosphors and their application to in vivo imaging of Caenorhabditis elegans. , 2011, Journal of materials chemistry.

[52]  Fu-ping Wang,et al.  Upconversion emission enhancement in Er3+/Yb3+-codoped BaTiO3 nanocrystals by tridoping with Li+ ions , 2011 .

[53]  Qingfeng Xiao,et al.  Dual-targeting upconversion nanoprobes across the blood-brain barrier for magnetic resonance/fluorescence imaging of intracranial glioblastoma. , 2014, ACS nano.

[54]  Zhen Cheng,et al.  In vitro and in vivo uncaging and bioluminescence imaging by using photocaged upconversion nanoparticles. , 2012, Angewandte Chemie.

[55]  Liangping Zhou,et al.  Radiopaque fluorescence-transparent TaOx decorated upconversion nanophosphors for in vivo CT/MR/UCL trimodal imaging. , 2012, Biomaterials.

[56]  W.G.J.H.M. van Sark,et al.  Enhanced near-infrared response of a-Si:H solar cells with β-NaYF4:Yb3+ (18%), Er3+ (2%) upconversion phosphors , 2010 .

[57]  Tymish Y. Ohulchanskyy,et al.  High contrast in vitro and in vivo photoluminescence bioimaging using near infrared to near infrared up-conversion in Tm3+ and Yb3+ doped fluoride nanophosphors. , 2008, Nano letters.

[58]  Liang Cheng,et al.  Multilayer dual-polymer-coated upconversion nanoparticles for multimodal imaging and serum-enhanced gene delivery. , 2013, ACS applied materials & interfaces.

[59]  A. Wilkinson,et al.  Delineating Mechanisms of Upconversion Enhancement by Li+ Codoping in Y2SiO5:Pr3+ , 2012 .

[60]  Qian Liu,et al.  High-efficiency upconversion luminescent sensing and bioimaging of Hg(II) by chromophoric ruthenium complex-assembled nanophosphors. , 2011, ACS nano.

[61]  Yun Sun,et al.  Fluorine-18 labeled rare-earth nanoparticles for positron emission tomography (PET) imaging of sentinel lymph node. , 2011, Biomaterials.

[62]  Yun Sun,et al.  Fluorine-18-labeled Gd3+/Yb3+/Er3+ co-doped NaYF4 nanophosphors for multimodality PET/MR/UCL imaging. , 2011, Biomaterials.

[63]  Zhipeng Li,et al.  Selective enhancement of green upconversion emissions of Er3+:Yb3Al5O12 nanocrystals by high excited state energy transfer with Yb3+–Mn2+ dimer sensitizing , 2012 .

[64]  Zhuang Liu,et al.  Upconversion nanophosphors for small-animal imaging. , 2012, Chemical Society reviews.

[65]  Yingxin Ma,et al.  Monodisperse upconversion NaYF4 nanocrystals: Syntheses and bioapplications , 2011 .

[66]  Y. Liu,et al.  Hydrothermal synthesis of NaLuF4:153Sm,Yb,Tm nanoparticles and their application in dual-modality upconversion luminescence and SPECT bioimaging. , 2013, Biomaterials.

[67]  M. Bawendi,et al.  Renal clearance of quantum dots , 2007, Nature Biotechnology.

[68]  Xin Zhang,et al.  One-pot hydrothermal synthesis of lanthanide ions doped one-dimensional upconversion submicrocrystals and their potential application in vivo CT imaging. , 2013, Nanoscale.

[69]  Nastassja A. Lewinski,et al.  Cytotoxicity of nanoparticles. , 2008, Small.

[70]  Yun Sun,et al.  Water-stable NaLuF4-based upconversion nanophosphors with long-term validity for multimodal lymphatic imaging. , 2012, Biomaterials.

[71]  Wei Feng,et al.  Radioisotope post-labeling upconversion nanophosphors for in vivo quantitative tracking. , 2013, Biomaterials.

[72]  Tianhong Pan,et al.  The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease. , 2008, Brain : a journal of neurology.

[73]  Xiu‐Ping Yan,et al.  Incorporation of computed tomography and magnetic resonance imaging function into NaYF4:Yb/Tm upconversion nanoparticles for in vivo trimodal bioimaging. , 2013, Analytical chemistry.

[74]  J. Dawes,et al.  Single-nanocrystal sensitivity achieved by enhanced upconversion luminescence. , 2013, Nature nanotechnology.

[75]  Shan Jiang,et al.  Upconversion nanoparticle-based FRET system for study of siRNA in live cells. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[76]  Jianhua Hao,et al.  PEG modified BaGdF₅:Yb/Er nanoprobes for multi-modal upconversion fluorescent, in vivo X-ray computed tomography and biomagnetic imaging. , 2012, Biomaterials.

[77]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[78]  Taeghwan Hyeon,et al.  Long-term real-time tracking of lanthanide ion doped upconverting nanoparticles in living cells. , 2011, Angewandte Chemie.

[79]  Hans H Gorris,et al.  Photon-upconverting nanoparticles for optical encoding and multiplexing of cells, biomolecules, and microspheres. , 2013, Angewandte Chemie.

[80]  W. Soboyejo,et al.  Biofunctionalization, cytotoxicity, and cell uptake of lanthanide doped hydrophobically ligated NaYF4 upconversion nanophosphors , 2008 .

[81]  Kai Yang,et al.  Highly-sensitive multiplexed in vivo imaging using pegylated upconversion nanoparticles , 2010 .

[82]  Daniel J. Klionsky,et al.  Autophagy fights disease through cellular self-digestion , 2008, Nature.

[83]  S. Laurent,et al.  High Relaxivities and Strong Vascular Signal Enhancement for NaGdF4 Nanoparticles Designed for Dual MR/Optical Imaging , 2013, Advanced healthcare materials.

[84]  Yu Saito,et al.  Design of poly(ethylene glycol)/streptavidin coimmobilized upconversion nanophosphors and their application to fluorescence biolabeling. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[85]  Zhuang Liu,et al.  Multicolor In Vivo Imaging of Upconversion Nanoparticles with Emissions Tuned by Luminescence Resonance Energy Transfer , 2011 .

[86]  Paras N. Prasad,et al.  (α-NaYbF4:Tm(3+))/CaF2 core/shell nanoparticles with efficient near-infrared to near-infrared upconversion for high-contrast deep tissue bioimaging. , 2012, ACS nano.

[87]  Wei Feng,et al.  Water-soluble lanthanide upconversion nanophosphors: Synthesis and bioimaging applications in vivo , 2014 .

[88]  Ralph Weissleder,et al.  Upconverting luminescent nanomaterials: application to in vivo bioimaging. , 2009, Chemical communications.

[89]  Brandon Da Silva,et al.  Intra-arterial infusion of PEGylated upconversion nanophosphors to improve the initial uptake by tumors in vivo , 2014 .

[90]  Jun Lin,et al.  Recent progress in rare earth micro/nanocrystals: soft chemical synthesis, luminescent properties, and biomedical applications. , 2014, Chemical reviews.

[91]  Yanqing Hua,et al.  Multifunctional nanoprobes for upconversion fluorescence, MR and CT trimodal imaging. , 2012, Biomaterials.

[92]  Lina Zhao,et al.  Enhanced red emission from GdF3:Yb3+,Er3+ upconversion nanocrystals by Li+ doping and their application for bioimaging. , 2012, Chemistry.

[93]  Liangping Zhou,et al.  Controlled synthesis of uniform and monodisperse upconversion core/mesoporous silica shell nanocomposites for bimodal imaging. , 2012, Chemistry.

[94]  Kim L R Brouwer,et al.  Methods to evaluate biliary excretion of drugs in humans: an updated review. , 2006, Molecular pharmaceutics.

[95]  Zhi-Gang Chen,et al.  Synthesis, characterization, and in vivo targeted imaging of amine-functionalized rare-earth up-converting nanophosphors. , 2009, Biomaterials.

[96]  U. Schubert,et al.  Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. , 2010, Angewandte Chemie.

[97]  Xiaogang Liu,et al.  Recent advances in the chemistry of lanthanide-doped upconversion nanocrystals. , 2009, Chemical Society reviews.

[98]  Zhaohua Jiang,et al.  Enhancement of the upconversion luminescence intensity in Er3+ doped BaTiO3 nanocrystals by codoping with Li+ ions , 2011 .

[99]  Shuhong Yu,et al.  PEGylated upconverting luminescent hollow nanospheres for drug delivery and in vivo imaging. , 2013, Small.

[100]  Christopher McRae,et al.  Upconversion luminescence with tunable lifetime in NaYF4:Yb,Er nanocrystals: role of nanocrystal size. , 2013, Nanoscale.

[101]  Paras N. Prasad,et al.  Monodisperse NaYbF4:Tm3+/NaGdF4 core/shell nanocrystals with near-infrared to near-infrared upconversion photoluminescence and magnetic resonance properties. , 2011, Nanoscale.

[102]  Jun Lin,et al.  Electrospinning Preparation and Drug‐Delivery Properties of an Up‐conversion Luminescent Porous NaYF4:Yb3+, Er3+@Silica Fiber Nanocomposite , 2011 .

[103]  Jianhua Hao,et al.  In vitro cell imaging using multifunctional small sized KGdF4:Yb3+,Er3+ upconverting nanoparticles synthesized by a one-pot solvothermal process. , 2013, Nanoscale.

[104]  Yong Zhang,et al.  Singlet oxygen-induced apoptosis of cancer cells using upconversion fluorescent nanoparticles as a carrier of photosensitizer. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[105]  Fuyou Li,et al.  Multimodal-luminescence core-shell nanocomposites for targeted imaging of tumor cells. , 2009, Chemistry.

[106]  Yibin Kang,et al.  Pegylated Composite Nanoparticles Containing Upconverting Phosphors and meso‐Tetraphenyl porphine (TPP) for Photodynamic Therapy , 2011 .

[107]  Kai Yang,et al.  In vivo pharmacokinetics, long-term biodistribution and toxicology study of functionalized upconversion nanoparticles in mice. , 2011, Nanomedicine.

[108]  Yanqing Hua,et al.  A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy. , 2013, Journal of the American Chemical Society.

[109]  Taeghwan Hyeon,et al.  Endocytosis, intracellular transport, and exocytosis of lanthanide-doped upconverting nanoparticles in single living cells. , 2012, Biomaterials.

[110]  Sandra L. Schmid,et al.  Regulated portals of entry into the cell , 2003, Nature.

[111]  Ququan Wang,et al.  Neurotoxin-conjugated upconversion nanoprobes for direct visualization of tumors under near-infrared irradiation. , 2010, Biomaterials.

[112]  H. Virgin,et al.  Autophagy in immunity and inflammation , 2011, Nature.

[113]  W. Lu,et al.  Simultaneous synthesis and amine-functionalization of single-phase BaYF5:Yb/Er nanoprobe for dual-modal in vivo upconversion fluorescence and long-lasting X-ray computed tomography imaging. , 2013, Nanoscale.

[114]  Wei Feng,et al.  Blue-emissive upconversion nanoparticles for low-power-excited bioimaging in vivo. , 2012, Journal of the American Chemical Society.

[115]  Shuk Han Cheng,et al.  Polymer-coated NaYF₄:Yb³⁺, Er³⁺ upconversion nanoparticles for charge-dependent cellular imaging. , 2011, ACS nano.

[116]  Manoj Kumar,et al.  Versatile photosensitizers for photodynamic therapy at infrared excitation. , 2007, Journal of the American Chemical Society.

[117]  Liang Yan,et al.  Mn2+ Dopant‐Controlled Synthesis of NaYF4:Yb/Er Upconversion Nanoparticles for in vivo Imaging and Drug Delivery , 2012, Advanced materials.

[118]  M. Samoć,et al.  Giant enhancement of upconversion in ultra-small Er3+/Yb3+:NaYF4 nanoparticles via laser annealing , 2012, Nanotechnology.

[119]  Zhuang Liu,et al.  Near-infrared light induced in vivo photodynamic therapy of cancer based on upconversion nanoparticles. , 2011, Biomaterials.

[120]  P. Choyke,et al.  Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. , 2008, Nanomedicine.

[121]  Andrew G. Glen,et al.  APPL , 2001 .

[122]  Liangping Zhou,et al.  Simultaneous nuclear imaging and intranuclear drug delivery by nuclear-targeted multifunctional upconversion nanoprobes. , 2012, Biomaterials.

[123]  B. Fei,et al.  Dual-modal fluorescent/magnetic bioprobes based on small sized upconversion nanoparticles of amine-functionalized BaGdF5:Yb/Er. , 2012, Nanoscale.

[124]  Daxiang Cui,et al.  Toxicity Assessments of Near-infrared Upconversion Luminescent LaF3:Yb,Er in Early Development of Zebrafish Embryos , 2013, Theranostics.

[125]  Yongsheng Liu,et al.  Lanthanide-doped luminescent nanoprobes: controlled synthesis, optical spectroscopy, and bioapplications. , 2013, Chemical Society reviews.

[126]  Weizhen Zeng,et al.  Structure, enhancement and white luminescence of multifunctional Lu₆O₅F₈:20%Yb³⁺,1%Er³⁺(Tm³⁺) nanoparticles via further doping with Li⁺ under different excitation sources. , 2013, Nanoscale.

[127]  Jianhua Hao,et al.  Simultaneous synthesis and functionalization of water-soluble up-conversion nanoparticles for in-vitro cell and nude mouse imaging. , 2011, Nanoscale.

[128]  Wei Feng,et al.  Core-shell Fe3O4@NaLuF4:Yb,Er/Tm nanostructure for MRI, CT and upconversion luminescence tri-modality imaging. , 2012, Biomaterials.

[129]  Wei Feng,et al.  Upconversion Nanophosphors Naluf4:Yb,Tm for Lymphatic Imaging In Vivo by Real-Time Upconversion Luminescence Imaging under Ambient Light and High-Resolution X-ray CT , 2013, Theranostics.

[130]  Yang Yang,et al.  Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors. , 2010, Biomaterials.

[131]  Fuyou Li,et al.  High contrast upconversion luminescence targeted imaging in vivo using peptide-labeled nanophosphors. , 2009, Analytical chemistry.

[132]  Nora Khanarian,et al.  In vivo and scanning electron microscopy imaging of up-converting nanophosphors in Caenorhabditis elegans. , 2006, Nano letters.

[133]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[134]  W. C. O'Neill,et al.  Contractile regulation of the Na(+)-K(+)-2Cl(-) cotransporter in vascular smooth muscle. , 2001, American journal of physiology. Cell physiology.

[135]  Xiuli Wang,et al.  Controlled synthesis and tunable luminescence of NaYF4:Eu3+ , 2010 .

[136]  X. Qu,et al.  DNA‐mediated Construction of Hollow Upconversion Nanoparticles for Protein Harvesting and Near‐Infrared Light Triggered Release , 2014, Advanced materials.

[137]  Huimao Zhang,et al.  Synthesis of NaYF4 : Yb3+, Er3+@ NaGdF4@ TaOx Multimodal Nanoprobe for Bioimaging Applications , 2013 .

[138]  Wei Feng,et al.  Gd3+ complex-modified NaLuF4-based upconversion nanophosphors for trimodality imaging of NIR-to-NIR upconversion luminescence, X-Ray computed tomography and magnetic resonance. , 2012, Biomaterials.

[139]  Wei Zhou,et al.  Tuning the autophagy-inducing activity of lanthanide-based nanocrystals through specific surface-coating peptides. , 2012, Nature materials.

[140]  Jun Lin,et al.  Multifunctional upconversion mesoporous silica nanostructures for dual modal imaging and in vivo drug delivery. , 2013, Small.

[141]  Meng Wang,et al.  Immunolabeling and NIR-excited fluorescent imaging of HeLa cells by using NaYF(4):Yb,Er upconversion nanoparticles. , 2009, ACS nano.

[142]  P. Prasad,et al.  Upconversion Nanoparticles: Design, Nanochemistry, and Applications in Theranostics , 2014, Chemical reviews.

[143]  Tymish Y. Ohulchanskyy,et al.  Combined Optical and MR Bioimaging Using Rare Earth Ion Doped NaYF4 Nanocrystals , 2009 .

[144]  Xueru Zhang,et al.  Optical thermometry through green and red upconversion emissions in Er3+/Yb3+/Li+:ZrO2 nanocrystals , 2011 .

[145]  Jun Lin,et al.  Synthesis of Li1−xNaxYF4:Yb3+/Ln3+ (0 ≤ x ≤ 0.3, Ln = Er, Tm, Ho) nanocrystals with multicolor up-conversion luminescence properties for in vitro cell imaging , 2012 .

[146]  Francesco Stellacci,et al.  Effect of surface properties on nanoparticle-cell interactions. , 2010, Small.

[147]  Dongmei Yang,et al.  Hollow structured upconversion luminescent NaYF₄:Yb³⁺, Er³⁺ nanospheres for cell imaging and targeted anti-cancer drug delivery. , 2013, Biomaterials.

[148]  Yong Zhang,et al.  Biocompatibility of silica coated NaYF(4) upconversion fluorescent nanocrystals. , 2008, Biomaterials.

[149]  Xueru Zhang,et al.  The Effect of Li on the Spectrum of Er3+ in Li- and Er-Codoped ZnO Nanocrystals , 2008 .

[150]  Nayoun Won,et al.  Multiplexed near-infrared in vivo imaging complementarily using quantum dots and upconverting NaYF4:Yb3+,Tm3+ nanoparticles. , 2011, Chemical communications.

[151]  Yong Zhang,et al.  Upconversion fluorescence imaging of cells and small animals using lanthanide doped nanocrystals. , 2008, Biomaterials.

[152]  Lili Wang,et al.  Improved 800 nm emission of Tm³⁺ sensitized by Yb³⁺ and Ho³⁺ in β-NaYF₄ nanocrystals under 980 nm excitation. , 2012, Optics express.

[153]  Xiaogang Qu,et al.  Long-circulating Er3+-doped Yb2O3 up-conversion nanoparticle as an in vivo X-Ray CT imaging contrast agent. , 2012, Biomaterials.

[154]  Qian Liu,et al.  "Drawing" upconversion nanophosphors into water through host-guest interaction. , 2010, Chemical communications.

[155]  Neil Genzlinger.  A. and Q , 2006 .

[156]  Chuanbin Mao,et al.  NIR-responsive silica-coated NaYbF(4):Er/Tm/Ho upconversion fluorescent nanoparticles with tunable emission colors and their applications in immunolabeling and fluorescent imaging of cancer cells. , 2009, The journal of physical chemistry. C, Nanomaterials and interfaces.

[157]  C. S. Lim,et al.  Simultaneous phase and size control of upconversion nanocrystals through lanthanide doping , 2010, Nature.

[158]  F. Vetrone,et al.  Enhancing upconverted white light in Tm3+/Yb3+/Ho3+-doped GdVO4 nanocrystals via incorporation of Li+ ions. , 2012, Optics express.

[159]  W. Marsden.  I and J , 2012 .

[160]  Juan Wang,et al.  Direct evidence of a surface quenching effect on size-dependent luminescence of upconversion nanoparticles. , 2010, Angewandte Chemie.

[161]  Qian Liu,et al.  A general strategy for biocompatible, high-effective upconversion nanocapsules based on triplet-triplet annihilation. , 2013, Journal of the American Chemical Society.

[162]  Xiu‐Ping Yan,et al.  One-step solvothermal synthesis of targetable optomagnetic upconversion nanoparticles for in vivo bimodal imaging. , 2013, Analytical chemistry.

[163]  Mingyuan Gao,et al.  Magnetic/upconversion fluorescent NaGdF4:Yb,Er nanoparticle-based dual-modal molecular probes for imaging tiny tumors in vivo. , 2013, ACS nano.

[164]  Dongmei Yang,et al.  Ultra-small BaGdF5-based upconversion nanoparticles as drug carriers and multimodal imaging probes. , 2014, Biomaterials.

[165]  R. Austin,et al.  Synthesis of Stable Block-Copolymer-Protected NaYF4:Yb3+, Er3+ Up-Converting Phosphor Nanoparticles , 2010 .

[166]  Taeghwan Hyeon,et al.  Theranostic Probe Based on Lanthanide‐Doped Nanoparticles for Simultaneous In Vivo Dual‐Modal Imaging and Photodynamic Therapy , 2012, Advanced materials.

[167]  Yanqing Hua,et al.  A NaYbF4: Tm3+ nanoprobe for CT and NIR-to-NIR fluorescent bimodal imaging. , 2012, Biomaterials.

[168]  Charalambos Kaittanis,et al.  Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. , 2010, ACS nano.