Lanthanide-doped up-converting nanoparticles: Merits and challenges

Summary Due to exceptional photo-physical properties, up-converting nanoparticles (UCNPs) are promising and advantageous alternative to conventional fluorescent labels used in many bio-medical applications. The first part of this review aims at presenting these properties as well as the current state-of-the-art in the up-conversion enhancement, NPs surface functionalization and bioconjugation. In the second part of the paper, the applications of UCNPs and currently available detection instrumentation are discussed in the view of the distinctive properties of these markers. Because the growing widespread use of the biofunctionalized NPs, scarce instrumentation for up-conversion detection is reviewed. Finally, the challenges and future perspectives of the UCNPs are discussed.

[1]  S. Gambhir,et al.  Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics , 2005, Science.

[2]  Yi Zhang,et al.  One-pot synthesis and strong near-infrared upconversion luminescence of poly(acrylic acid)-functionalized YF3:Yb3+/Er3+ nanocrystals , 2010 .

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

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

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

[6]  N. J. Johnson,et al.  Facile ligand-exchange with polyvinylpyrrolidone and subsequent silica coating of hydrophobic upconverting beta-NaYF(4):Yb(3+)/Er(3+) nanoparticles. , 2010, Nanoscale.

[7]  James A. Piper,et al.  Visible-light-sensitized highly luminescent europium nanoparticles: preparation and application for time-gated luminescence bioimaging , 2009 .

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

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

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

[11]  T. Soukka,et al.  Homogeneous noncompetitive immunoassay for 17beta-estradiol based on fluorescence resonance energy transfer. , 2007, Analytical chemistry.

[12]  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.

[13]  Wenjun Zhao,et al.  Bioconjugated silica nanoparticles: Development and applications , 2008 .

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

[15]  Denis Boudreau,et al.  FRET enhancement in multilayer core-shell nanoparticles. , 2009, Nano letters.

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

[17]  G. Chow,et al.  Synthesis of Hexagonal‐Phase NaYF4:Yb,Er and NaYF4:Yb,Tm Nanocrystals with Efficient Up‐Conversion Fluorescence , 2006 .

[18]  C. D. Geddes,et al.  Editorial: Metal-Enhanced Fluorescence , 2002, Journal of Fluorescence.

[19]  Zhengping Li,et al.  Surface modification of hydrophobic NaYF4:Yb,Er upconversion nanophosphors and their applications for immunoassay , 2011 .

[20]  K. Uvdal,et al.  Synthesis and Characterization of Tb3+-Doped Gd2O3 Nanocrystals : A Bifunctional Material with Combined Fluorescent Labeling and MRI Contrast Agent Properties , 2009 .

[21]  Dan Wang,et al.  Using 915 nm laser excited Tm³+/Er³+/Ho³+- doped NaYbF4 upconversion nanoparticles for in vitro and deeper in vivo bioimaging without overheating irradiation. , 2011, ACS nano.

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

[23]  A. Patra,et al.  Impacts of core-shell structures on properties of lanthanide-based nanocrystals: crystal phase, lattice strain, downconversion, upconversion and energy transfer. , 2012, Nanoscale.

[24]  Yujie Xiong,et al.  Modification of NaYF4:Yb,Er@SiO2 Nanoparticles with Gold Nanocrystals for Tunable Green-to-Red Upconversion Emissions , 2011 .

[25]  M. Mycek,et al.  Handbook of Biomedical Fluorescence , 2003 .

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

[27]  Kai Yang,et al.  Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy. , 2012, Biomaterials.

[28]  Jiao Chen,et al.  Upconversion Nanomaterials: Synthesis, Mechanism, and Applications in Sensing , 2012, Sensors.

[29]  Hisataka Kobayashi,et al.  Multiplexed imaging in cancer diagnosis: applications and future advances. , 2010, The Lancet. Oncology.

[30]  Yan Li,et al.  Dopant-controlled synthesis of water-soluble hexagonal NaYF4 nanorods with efficient upconversion fluorescence for multicolor bioimaging , 2010 .

[31]  K. Uvdal,et al.  Synthesis and characterisation of Gd2O3 nanocrystals functionalised by organic acids. , 2005, Journal of colloid and interface science.

[32]  Aijun Zeng,et al.  A Simple Optical Reader for Upconverting Phosphor Particles Captured on Lateral Flow Strip , 2009, IEEE Sensors Journal.

[33]  S. Hell,et al.  Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. , 1994, Optics letters.

[34]  Fuyou Li,et al.  Versatile synthesis strategy for carboxylic acid-functionalized upconverting nanophosphors as biological labels. , 2008, Journal of the American Chemical Society.

[35]  G. Lowry,et al.  Towards a definition of inorganic nanoparticles from an environmental, health and safety perspective. , 2009, Nature nanotechnology.

[36]  C. Bremer,et al.  Labeling of Anti-MUC-1 Binding Single Chain Fv Fragments to Surface Modified Upconversion Nanoparticles for an Initial in Vivo Molecular Imaging Proof of Principle Approach , 2012, International journal of molecular sciences.

[37]  Chaoyang Jiang,et al.  Layer-by-layer assembly of freestanding thin films with homogeneously distributed upconversion nanocrystals , 2010 .

[38]  Zhang Yong,et al.  Upconverting nanoparticles as nanotransducers for photodynamic therapy in cancer cells. , 2008, Nanomedicine.

[39]  Ming Liu,et al.  Recent advances in synthesis and surface modification of lanthanide-doped upconversion nanoparticles for biomedical applications. , 2012, Biotechnology advances.

[40]  E. Rosa,et al.  Enhancement of Upconversion Emission of LaPO4:Er@Yb Core−Shell Nanoparticles/Nanorods , 2008 .

[41]  F. Huang,et al.  Dopant-induced phase transition: a new strategy of synthesizing hexagonal upconversion NaYF4 at low temperature. , 2011, Chemical communications.

[42]  Daniel Jaque,et al.  Nanoparticles for highly efficient multiphoton fluorescence bioimaging. , 2010, Optics express.

[43]  Lanlan Zhong,et al.  Enhancement of Near-Infrared-to-Visible Upconversion Luminescence Using Engineered Plasmonic Gold Surfaces , 2011 .

[44]  Zhuang Liu,et al.  Multiplexed five-color molecular imaging of cancer cells and tumor tissues with carbon nanotube Raman tags in the near-infrared , 2010, Nano research.

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

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

[47]  M. McHenry,et al.  Evaluation of iron-cobalt/ferrite core-shell nanoparticles for cancer thermotherapy , 2008 .

[48]  Jie Shen,et al.  Rare-Earth nanoparticles with enhanced upconversion emission and suppressed rare-Earth-ion leakage. , 2012, Chemistry.

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

[50]  Mingdong Huang,et al.  Amine-functionalized lanthanide-doped KGdF4 nanocrystals as potential optical/magnetic multimodal bioprobes. , 2012, Journal of the American Chemical Society.

[51]  Lian Li,et al.  Multicolor output and shape controlled synthesis of lanthanide-ion doped fluorides upconversion nanoparticles. , 2011, Dalton transactions.

[52]  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.

[53]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

[54]  O. Wolfbeis,et al.  Upconverting luminescent nanoparticles for use in bioconjugation and bioimaging. , 2010, Current opinion in chemical biology.

[55]  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.

[56]  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.

[57]  M. Haase,et al.  Highly Efficient Multicolour Upconversion Emission in Transparent Colloids of Lanthanide‐Doped NaYF4 Nanocrystals , 2004 .

[58]  Louis A. Cuccia,et al.  Controlled Synthesis and Water Dispersibility of Hexagonal Phase NaGdF4:Ho3+/Yb3+ Nanoparticles , 2009 .

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

[60]  Renren Deng,et al.  Tuning upconversion through energy migration in core-shell nanoparticles. , 2011, Nature materials.

[61]  Yin Min,et al.  Upconversion luminescence enhancement in Yb3+/Tm3+-codoped Lu2O3 nanocrystals induced by doping with Li+ ions. , 2011, Journal of Nanoscience and Nanotechnology.

[62]  D. Zhao,et al.  Shape, size, and phase-controlled rare-Earth fluoride nanocrystals with optical up-conversion properties. , 2009, Chemistry.

[63]  Frank Caruso,et al.  Biofunctionalization of fluorescent rare-earth-doped lanthanum phosphate colloidal nanoparticles. , 2004, Angewandte Chemie.

[64]  Yu Huang,et al.  Plasmonic modulation of the upconversion fluorescence in NaYF4 :Yb/Tm hexaplate nanocrystals using gold nanoparticles or nanoshells. , 2010, Angewandte Chemie.

[65]  Hans H. Feindt,et al.  Multiphoton up-converting phosphors for use in rapid immunoassays , 2000, Photonics West - Biomedical Optics.

[66]  Kian Meng Lim,et al.  NIR-to-visible upconversion nanoparticles for fluorescent labeling and targeted delivery of siRNA , 2009, Nanotechnology.

[67]  Jun Lin,et al.  Core–Shell Structured Up-Conversion Luminescent and Mesoporous NaYF4:Yb3+/Er3+@nSiO2@mSiO2 Nanospheres as Carriers for Drug Delivery , 2011 .

[68]  A. Roda,et al.  Nanobioanalytical luminescence: Förster-type energy transfer methods , 2009, Analytical and bioanalytical chemistry.

[69]  R. Sam Niedbala,et al.  Up-converting phosphor reporters for nucleic acid microarrays , 2001, Nature Biotechnology.

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

[71]  Muriel Mari,et al.  Microscopy: Science, Technology, Applications and Education , 2010 .

[72]  Gregory S Harms,et al.  Upconverting nanoparticles for nanoscale thermometry. , 2011, Angewandte Chemie.

[73]  K. Krämer,et al.  Origin of the High Upconversion Green Luminescence Efficiency in β-NaYF4:2%Er3+,20%Yb3+ , 2011 .

[74]  吕强,et al.  Upconversion emission enhancement of TiO2 coated lanthanide-doped Y2O3 nanoparticles , 2009 .

[75]  孔祥贵,et al.  Critical shell thickness of core/shell upconversion luminescence nanoplatform… , 2011 .

[76]  Zhiyu Qian,et al.  Amphiphilic chitosan modified upconversion nanoparticles for in vivo photodynamic therapy induced by near-infrared light , 2012 .

[77]  Tero Soukka,et al.  Fluorescence-quenching-based enzyme-activity assay by using photon upconversion. , 2008, Angewandte Chemie.

[78]  Zhihong Liu,et al.  An effective approach to enhanced energy-transfer efficiency from up-converting phosphors and increased assay sensitivity. , 2012, Chemical communications.

[79]  D. Balding,et al.  HLA Sequence Polymorphism and the Origin of Humans , 2006 .

[80]  Z. L. Wang,et al.  Biofunctionalization of CeF3:Tb3+ nanoparticles , 2007, Nanotechnology.

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

[82]  Meng Wang,et al.  Upconversion nanoparticles: synthesis, surface modification and biological applications. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[83]  Hooisweng Ow,et al.  Bright and stable core-shell fluorescent silica nanoparticles. , 2005, Nano letters.

[84]  S. Rogelj,et al.  Design of a highly sensitive and specific nucleotide sensor based on photon upconverting particles. , 2006, Journal of the American Chemical Society.

[85]  J. M. Kikkawa,et al.  A generalized ligand-exchange strategy enabling sequential surface functionalization of colloidal nanocrystals. , 2011, Journal of the American Chemical Society.

[86]  J. Leroux,et al.  Poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) as a new polymeric solubilizer for hydrophobic anticancer drugs: in vitro and in vivo evaluation. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[87]  Frank C J M van Veggel,et al.  Surface modification of upconverting NaYF4 nanoparticles with PEG-phosphate ligands for NIR (800 nm) biolabeling within the biological window. , 2010, Langmuir : the ACS journal of surfaces and colloids.

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

[89]  Daniel Malamud,et al.  Rapid Assay Format for Multiplex Detection of Humoral Immune Responses to Infectious Disease Pathogens (HIV, HCV, and TB) , 2007, Annals of the New York Academy of Sciences.

[90]  Zhigang Chen,et al.  Laser scanning up-conversion luminescence microscopy for imaging cells labeled with rare-earth nanophosphors. , 2009, Analytical chemistry.

[91]  Kerry R. Delaney,et al.  Two-Photon Upconversion Laser (Scanning and Wide-Field) Microscopy Using Ln3+-Doped NaYF4 Upconverting Nanocrystals: A Critical Evaluation of their Performance and Potential in Bioimaging , 2011 .

[92]  William S Ryu,et al.  Particle size dependence of the dynamic photophysical properties of NaYF4:Yb, Er nanocrystals. , 2010, Optics express.

[93]  Richard Perron,et al.  Eu3+-doped Gd2O3 nanoparticles as reporters for optical detection and visualization of antibodies patterned by microcontact printing , 2006, Analytical and bioanalytical chemistry.

[94]  Otto S. Wolfbeis,et al.  Upconverting nanoparticle based optical sensor for carbon dioxide , 2010 .

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

[96]  F. Auzel,et al.  Materials and devices using double-pumped-phosphors with energy transfer , 1973 .

[97]  John-Christopher Boyer,et al.  Synthesis of colloidal upconverting NaYF4: Er3+/Yb3+ and Tm3+/Yb3+ monodisperse nanocrystals. , 2006, Nano letters.

[98]  Guicheng Jiang,et al.  An effective polymer cross-linking strategy to obtain stable dispersions of upconverting NaYF4 nanoparticles in buffers and biological growth media for biolabeling applications. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[99]  Wei Feng,et al.  Luminescent chemodosimeters for bioimaging. , 2013, Chemical reviews.

[100]  Tierui Zhang,et al.  A general approach for transferring hydrophobic nanocrystals into water. , 2007, Nano letters.

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

[102]  D. Wawrzyńczyk,et al.  Synthesis and spectral properties of colloidal Nd3+ doped NaYF4 nanocrystals , 2011 .

[103]  Stefan Andersson-Engels,et al.  Autofluorescence insensitive imaging using upconverting nanocrystals in scattering media , 2008 .

[104]  Lehui Lu,et al.  Dual modal in vivo imaging using upconversion luminescence and enhanced computed tomography properties. , 2011, Nanoscale.

[105]  Hong Zhang,et al.  Controlled synthesis, formation mechanism, and great enhancement of red upconversion luminescence of NaYF4:Yb3+, Er3+ nanocrystals/submicroplates at low doping level. , 2008, The journal of physical chemistry. B.

[106]  Peter A. Williams,et al.  Inhibition of Protein Adsorption onto Silica by Polyvinylpyrrolidone , 2002 .

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

[108]  Qingqing Dou,et al.  Tuning of the structure and emission spectra of upconversion nanocrystals by alkali ion doping. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[109]  W. Stöber,et al.  Controlled growth of monodisperse silica spheres in the micron size range , 1968 .

[110]  Tero Soukka,et al.  Photochemical Characterization of Up-Converting Inorganic Lanthanide Phosphors as Potential Labels , 2005, Journal of Fluorescence.

[111]  Oliver Benson,et al.  Observation of size dependence in multicolor upconversion in single Yb3+, Er3+ Codoped NaYF4 nanocrystals. , 2009, Nano letters.

[112]  Zai-xin Liu,et al.  Upconversion nanoparticles modified with aminosilanes as carriers of DNA vaccine for foot-and-mouth disease , 2012, Applied Microbiology and Biotechnology.

[113]  Hui Guo,et al.  Mesoporous-silica-coated up-conversion fluorescent nanoparticles for photodynamic therapy. , 2009, Small.

[114]  Zhengwei Pan,et al.  Lanthanide-doped GdVO4 upconversion nanophosphors with tunable emissions and their applications for biomedical imaging , 2012 .

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

[116]  M. Dyrba,et al.  Effect of pH on the synthesis and properties of luminescent SiO2/calcium phosphate:Eu3+ core-shell nanoparticles. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[117]  P. Perriat,et al.  Functionalization of luminescent aminated particles for facile bioconjugation. , 2008, ACS nano.

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

[119]  Yadong Li,et al.  Luminescent nanocrystals for nonenzymatic glucose concentration determination. , 2007, Chemistry.

[120]  Y. Harada,et al.  Intracellular temperature mapping with a fluorescent polymeric thermometer and fluorescence lifetime imaging microscopy , 2012, Nature Communications.

[121]  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.

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

[123]  Tian Ming,et al.  Plasmon-Controlled Förster Resonance Energy Transfer , 2012 .

[124]  Wing-Cheung Law,et al.  Core/shell NaGdF4:Nd(3+)/NaGdF4 nanocrystals with efficient near-infrared to near-infrared downconversion photoluminescence for bioimaging applications. , 2012, ACS nano.

[125]  Feng Wang,et al.  Synthesis of polyethylenimine/NaYF4 nanoparticles with upconversion fluorescence , 2006 .

[126]  John R. Crowther,et al.  The ELISA Guidebook , 2000, Methods in Molecular Biology™.

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

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

[129]  N. Browning,et al.  Plasmonic enhanced emissions from cubic NaYF(4):Yb: Er/Tm nanophosphors. , 2011, Chemistry of materials : a publication of the American Chemical Society.

[130]  Ya-Wen Zhang,et al.  Highly Efficient Multicolor Up-Conversion Emissions and Their Mechanisms of Monodisperse NaYF4:Yb,Er Core and Core/Shell-Structured Nanocrystals , 2007 .

[131]  Paras N. Prasad,et al.  Introduction to Nanomedicine and Nanobioengineering , 2012 .

[132]  D. Xing,et al.  Pyropheophorbide A and c(RGDyK) comodified chitosan-wrapped upconversion nanoparticle for targeted near-infrared photodynamic therapy. , 2012, Molecular pharmaceutics.

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

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

[135]  Ignacy Gryczynski,et al.  Metal-enhanced fluorescence: an emerging tool in biotechnology. , 2005, Current opinion in biotechnology.

[136]  R. Nitschke,et al.  Quantum dots versus organic dyes as fluorescent labels , 2008, Nature Methods.

[137]  Pekka Hänninen,et al.  Multiple sized europium(III) chelate-dyed polystyrene particles as donors in FRET - an application for sensitive protein quantification utilizing competitive adsorption. , 2009, The Analyst.

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

[139]  Chunya Li,et al.  Upconversion fluorescence resonance energy transfer based biosensor for ultrasensitive detection of matrix metalloproteinase-2 in blood. , 2012, Analytical chemistry.

[140]  F. V. van Veggel,et al.  Silica-coated Ln3+-Doped LaF3 nanoparticles as robust down- and upconverting biolabels. , 2006, Chemistry.

[141]  Paul N Manson,et al.  Variable cytocompatibility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation. , 2005, Biomaterials.

[142]  Weihong Tan,et al.  Multicolor FRET silica nanoparticles by single wavelength excitation. , 2006, Nano letters.

[143]  Lu Qiang,et al.  Upconversion emission enhancement of TiO 2 coated lanthanide-doped Y 2 O 3 nanoparticles , 2009 .

[144]  Hong Zhang,et al.  Hexanedioic acid mediated surface-ligand-exchange process for transferring NaYF4:Yb/Er (or Yb/Tm) up-converting nanoparticles from hydrophobic to hydrophilic. , 2009, Journal of colloid and interface science.

[145]  Shuping Xu,et al.  Near-Infrared Fluorescent Materials for Sensing of Biological Targets , 2008, Sensors.

[146]  Kai Yang,et al.  Facile preparation of multifunctional upconversion nanoprobes for multimodal imaging and dual-targeted photothermal therapy. , 2011, Angewandte Chemie.

[147]  Zhiguo Zhang,et al.  Upconversion emission tuning from green to red in Yb3+/Ho3+-codoped NaYF4 nanocrystals by tridoping with Ce3+ ions , 2009, Nanotechnology.

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

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

[150]  Renfu Li,et al.  Time-resolved FRET biosensor based on amine-functionalized lanthanide-doped NaYF4 nanocrystals. , 2011, Angewandte Chemie.

[151]  Zhuang Liu,et al.  Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy. , 2011, Biomaterials.

[152]  Wei Li,et al.  Direct imaging the upconversion nanocrystal core/shell structure at the subnanometer level: shell thickness dependence in upconverting optical properties. , 2012, Nano letters.

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

[154]  Thierry Gacoin,et al.  Biological applications of rare-earth based nanoparticles. , 2011, ACS nano.

[155]  J. Bünzli,et al.  Increasing the efficiency of lanthanide luminescent bioprobes: bioconjugated silica nanoparticles as markers for cancerous cells , 2010 .

[156]  Zhuang Liu,et al.  Polymer encapsulated upconversion nanoparticle/iron oxide nanocomposites for multimodal imaging and magnetic targeted drug delivery. , 2011, Biomaterials.

[157]  Yueqing Gu,et al.  Comparison of Two Strategies for the Synthesis of Upconverting Nanoparticles as Biological labels , 2011 .

[158]  T. Soukka,et al.  Upconversion fluorescence enables homogeneous immunoassay in whole blood. , 2007, Clinical chemistry.

[159]  Vijaya K. Mokkapati,et al.  Evaluation of UPlink–RSV , 2007, Annals of the New York Academy of Sciences.

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

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

[162]  Michael W. Davidson,et al.  The fluorescent protein palette: tools for cellular imaging. , 2009, Chemical Society reviews.

[163]  Fang Wang,et al.  Multifunctional core-shell upconverting nanoparticles for imaging and photodynamic therapy of liver cancer cells. , 2012, Chemistry, an Asian journal.

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

[165]  Xinxiang Zhang,et al.  Bioconjugation of functionalized fluorescent YVO(4):Eu nanocrystals with BSA for immunoassay. , 2007, Talanta.

[166]  O. Wolfbeis,et al.  Optical ammonia sensor based on upconverting luminescent nanoparticles. , 2010, Analytical chemistry.

[167]  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.

[168]  Manoj Kumar,et al.  Highly sensitive and selective label-free optical detection of DNA hybridization based on photon upconverting nanoparticles. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[169]  Yue Tian,et al.  Bio-conjugation of CaF2:Eu/chitosan nanoparticles with BSA and photoluminescent properties , 2009 .

[170]  Christopher G. Morgan,et al.  The Active‐Core/Active‐Shell Approach: A Strategy to Enhance the Upconversion Luminescence in Lanthanide‐Doped Nanoparticles , 2009 .

[171]  Yuan Gao,et al.  Water-soluble NaYF4:Yb/Er upconversion nanophosphors: Synthesis, characteristics and application in bioimaging , 2010 .

[172]  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.

[173]  Ralph Weissleder,et al.  Near-infrared fluorescence: application to in vivo molecular imaging. , 2010, Current opinion in chemical biology.

[174]  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.

[175]  翁文桂,et al.  Advances in the Surface Engineering of Upconversion Nanocrystals , 2012 .

[176]  F. V. van Veggel,et al.  Bioconjugation of Ln3+-doped LaF3 nanoparticles to avidin. , 2006, Langmuir : the ACS journal of surfaces and colloids.

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

[178]  Feng Wang,et al.  One-pot synthesis of chitosan/LaF3:Eu3+ nanocrystals for bio-applications , 2006, Nanotechnology.

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

[180]  M. Wilchek,et al.  The avidin-biotin complex in bioanalytical applications. , 1988, Analytical biochemistry.

[181]  Gan-Moog Chow,et al.  Water -soluble NaYF4:Yb,Er (Tm)/NaYF4/Polymer Core/Shell/Shell nanoparticles with significant enhancement of upconversion fluorescence , 2007 .

[182]  J. Bünzli.  Lanthanide luminescence for biomedical analyses and imaging. , 2010, Chemical reviews.

[183]  Bruce D Hammock,et al.  Microarray immunoassay for phenoxybenzoic acid using polymer encapsulated Eu:Gd2O3 nanoparticles as fluorescent labels. , 2005, Analytical chemistry.

[184]  A. Kaminskiĭ,et al.  Crystalline Lasers: Physical Processes and Operating Schemes , 1996 .

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

[186]  M. Samoć,et al.  Modulation of up-conversion luminescence of lanthanide(III) ion co-doped NaYF4 nanoparticles using gold nanorods , 2012 .

[187]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[188]  Chun-Hua Yan,et al.  Clean and Flexible Modification Strategy for Carboxyl/Aldehyde‐Functionalized Upconversion Nanoparticles and Their Optical Applications , 2009 .

[189]  Matthias I. J. Stich,et al.  pH sensor based on upconverting luminescent lanthanide nanorods. , 2009, Chemical communications.

[190]  Yong Zhang,et al.  Upconversion fluorescent nanoparticles as a potential tool for in-depth imaging , 2011, Nanotechnology.

[191]  G. Kovacs,et al.  Evolving point-of-care diagnostics using up-converting phosphor bioanalytical systems. , 2009, Analytical chemistry.

[192]  S. Nie,et al.  Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules , 2001, Nature Biotechnology.

[193]  R. Clegg.  Fluorescence resonance energy transfer. , 2020, Current Opinion in Biotechnology.

[194]  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.

[195]  Qing Peng,et al.  Fluorescence resonant energy transfer biosensor based on upconversion-luminescent nanoparticles. , 2005, Angewandte Chemie.

[196]  Marco Bettinelli,et al.  Significance of Yb3+ concentration on the upconversion mechanisms in codoped Y2O3:Er3+, Yb3+ nanocrystals , 2004 .

[197]  Qian Liu,et al.  Iridium(III) complex-coated nanosystem for ratiometric upconversion luminescence bioimaging of cyanide anions. , 2011, Journal of the American Chemical Society.

[198]  Tero Soukka,et al.  Homogeneous assay technology based on upconverting phosphors. , 2005, Analytical chemistry.

[199]  Chunhua Yan,et al.  Luminescent rare earth nanomaterials for bioprobe applications. , 2008, Dalton transactions.

[200]  D. Wawrzyńczyk,et al.  Optically stimulated heating using Nd3+ doped NaYF4 colloidal near infrared nanophosphors , 2011 .

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

[202]  Francisco Sanz-Rodríguez,et al.  Temperature sensing using fluorescent nanothermometers. , 2010, ACS nano.

[203]  Xueyuan Chen,et al.  Upconversion nanoparticles in biological labeling, imaging, and therapy. , 2010, The Analyst.

[204]  H Tanke,et al.  Use of up-converting phosphor reporters in lateral-flow assays to detect specific nucleic acid sequences: a rapid, sensitive DNA test to identify human papillomavirus type 16 infection. , 2001, Clinical chemistry.

[205]  Oliver Benson,et al.  Plasmon-enhanced upconversion in single NaYF4:Yb3+/Er3+ codoped nanocrystals. , 2010, Nano letters.

[206]  H. Tanke,et al.  Up-Converting Phosphor Technology-Based Lateral Flow Assay for Detection of Schistosoma Circulating Anodic Antigen in Serum , 2007, Journal of Clinical Microbiology.

[207]  Zhuang Liu,et al.  Research Spotlight: Upconversion nanoparticles for potential cancer theranostics , 2011 .

[208]  Jun Chen,et al.  Morphologically controlled synthesis of colloidal upconversion nanophosphors and their shape-directed self-assembly , 2010, Proceedings of the National Academy of Sciences.

[209]  Nuo Duan,et al.  Dual-color upconversion fluorescence and aptamer-functionalized magnetic nanoparticles-based bioassay for the simultaneous detection of Salmonella Typhimurium and Staphylococcus aureus. , 2012, Analytica chimica acta.

[210]  T. Soukka,et al.  Photon Upconversion in Homogeneous Fluorescence‐based Bioanalytical Assays , 2008, Annals of the New York Academy of Sciences.

[211]  J. Boilot,et al.  High Up-Conversion Efficiency of YVO4:Yb,Er Nanoparticles in Water down to the Single-Particle Level , 2010 .

[212]  Young Min Kim,et al.  Development of an ultrarapid one-step fluorescence immunochromatographic assay system for the quantification of microcystins. , 2003, Environmental science & technology.

[213]  H. Too,et al.  Gold decorated NaYF4:Yb,Er/NaYF4/silica (core/shell/shell) upconversion nanoparticles for photothermal destruction of BE(2)-C neuroblastoma cells , 2011 .

[214]  J. Ying,et al.  Reverse microemulsion-mediated synthesis of silica-coated gold and silver nanoparticles. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[215]  Ron C. Hardman.  A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors , 2005, Environmental health perspectives.

[216]  S. Nie,et al.  Quantum dot nanocrystals for in vivo molecular and cellular imaging. , 2004, Photochemistry and photobiology.

[217]  Marco Pedroni,et al.  NIR-to-NIR two-photon excited CaF2:Tm3+,Yb3+ nanoparticles: multifunctional nanoprobes for highly penetrating fluorescence bio-imaging. , 2011, ACS nano.

[218]  J. Burton,et al.  Detection of analytes by immunoassay using up-converting phosphor technology. , 2001, Analytical biochemistry.

[219]  Hongwei Song,et al.  Influence of the TGA Modification on Upconversion Luminescence of Hexagonal-Phase NaYF4:Yb3+, Er3+ Nanoparticles , 2010 .

[220]  Jun Lin,et al.  Avidin conjugation to up-conversion phosphor NaYF4:Yb3+, Er3+ by the oxidation of the oligosaccharide chains , 2009 .

[221]  Zhouping Wang,et al.  Simultaneous detection of enterovirus 71 and coxsackievirus A16 using dual-colour upconversion luminescent nanoparticles as labels. , 2012, Chemical communications.

[222]  J. Jaiswal,et al.  Potentials and pitfalls of fluorescent quantum dots for biological imaging. , 2004, Trends in cell biology.

[223]  M. Sauer,et al.  A close look at fluorescence quenching of organic dyes by tryptophan. , 2005, Chemphyschem : a European journal of chemical physics and physical chemistry.

[224]  Ying Ran,et al.  Fabrication of and drug delivery by an upconversion emission nanocomposite with monodisperse LaF3:Yb,Er core / mesoporous silica shell structure , 2010 .

[225]  T. Soukka,et al.  Oligonucleotide array-in-well platform for detection and genotyping human adenoviruses by utilizing upconverting phosphor label technology. , 2011, Analytical chemistry.

[226]  Christian Eggeling,et al.  Macromolecular-scale resolution in biological fluorescence microscopy. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[227]  M. Pollnau,et al.  Near-infrared to visible photon upconversion processes in lanthanide doped chloride, bromide and iodide lattices , 2000 .

[228]  N. A. Mufti,et al.  Upconverting phosphor reporters in immunochromatographic assays. , 2001, Analytical biochemistry.

[229]  Meng Wang,et al.  Immunoassay of goat antihuman immunoglobulin G antibody based on luminescence resonance energy transfer between near-infrared responsive NaYF4:Yb, Er upconversion fluorescent nanoparticles and gold nanoparticles. , 2009, Analytical chemistry.