Recent Advances on Functionalized Upconversion Nanoparticles for Detection of Small Molecules and Ions in Biosystems

Abstract Significant progress on upconversion‐nanoparticle (UCNP)‐based probes is witnessed in recent years. Compared with traditional fluorescent probes (e.g., organic dyes, metal complexes, or inorganic quantum dots), UCNPs have many advantages such as non‐autofluorescence, high chemical stability, large light‐penetration depth, long lifetime, and less damage to samples. This article focuses on recent achievements in the usage of lanthanide‐doped UCNPs as efficient probes for biodetection since 2014. The mechanisms of upconversion as well as the luminescence resonance energy transfer process is introduced first, followed by a detailed summary on the recent researches of UCNP‐based biodetections including the detection of inorganic ions, gas molecules, reactive oxygen species, and thiols and hydrogen sulfide.

[1]  R. Yu,et al.  Fabrication of a LRET-based upconverting hybrid nanocomposite for turn-on sensing of H2O2 and glucose. , 2016, Nanoscale.

[2]  Xiao Cui,et al.  An ``off-on'' fluorescence probe for Hg(II) detection using upconversion nanobars as the excitation source: Preparation, characterization and sensing performance , 2014 .

[3]  Hongwei Song,et al.  Highly sensitive and selective detection of mercury ions based on up-conversion FRET from NaYF4:Yb3+/Er3+ nanophosphors to CdTe quantum dots , 2015 .

[4]  Jing Zhou,et al.  Ultrahigh Sensitivity Multifunctional Nanoprobe for the Detection of Hydroxyl Radical and Evaluation of Heavy Metal Induced Oxidative Stress in Live Hepatocyte. , 2017, Analytical chemistry.

[5]  Fuyou Li,et al.  Amphiphilic diarylethene as a photoswitchable probe for imaging living cells. , 2008, Journal of the American Chemical Society.

[6]  Cheng Zhang,et al.  Upconversion nanoparticles for ratiometric fluorescence detection of nitrite. , 2014, The Analyst.

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

[8]  Wei Feng,et al.  Yolk-shell upconversion nanocomposites for LRET sensing of cysteine/homocysteine. , 2014, ACS applied materials & interfaces.

[9]  Jianghong Rao,et al.  Quantum dot bioconjugates for in vitro diagnostics & in vivo imaging. , 2008, Cancer biomarkers : section A of Disease markers.

[10]  Claudia Felser,et al.  On the influence of bandstructure on transport properties of magnetic tunnel junctions with Co2Mn1−xFexSi single and multilayer electrode , 2008 .

[11]  J. Lannutti,et al.  Nanoscale upconversion for oxygen sensing. , 2017, Materials science & engineering. C, Materials for biological applications.

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

[13]  Qichun Zhang,et al.  Rhodamine-modified upconversion nanophosphors for ratiometric detection of hypochlorous acid in aqueous solution and living cells. , 2014, Small.

[14]  Wei Feng,et al.  Cyclometallated ruthenium complex-modified upconversion nanophosphors for selective detection of Hg2+ ions in water. , 2014, Nanoscale.

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

[16]  S. Yao,et al.  A Novel Fluorescent Biosensor for Detection of Silver Ions Based on Upconversion Nanoparticles , 2016, Journal of Fluorescence.

[17]  Zilong Wang,et al.  Azaacenes as active elements for sensing and bio applications. , 2016, Journal of materials chemistry. B.

[18]  Qingsong Mei,et al.  Oxidative cleavage-based upconversional nanosensor for visual evaluation of antioxidant activity of drugs. , 2015, Biosensors & bioelectronics.

[19]  Jianlin Shi,et al.  Sensitive imaging and effective capture of Cu(2+): Towards highly efficient theranostics of Alzheimer's disease. , 2016, Biomaterials.

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

[21]  M. S. Gonçalves,et al.  Fluorescent labeling of biomolecules with organic probes. , 2009, Chemical reviews.

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

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

[24]  Qiang Zhao,et al.  Dye-conjugated upconversion nanoparticles for ratiometric imaging of intracellular pH values , 2015 .

[25]  O. Wolfbeis,et al.  Luminescent sensing of oxygen using a quenchable probe and upconverting nanoparticles. , 2011, Angewandte Chemie.

[26]  Nuo Duan,et al.  Dual fluorescence resonance energy transfer assay between tunable upconversion nanoparticles and controlled gold nanoparticles for the simultaneous detection of Pb²⁺ and Hg²⁺. , 2014, Talanta.

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

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

[29]  Sami Koho,et al.  Photon upconversion sensitized nanoprobes for sensing and imaging of pH. , 2014, Nanoscale.

[30]  Zhihong Liu,et al.  Modulating the Luminescence of Upconversion Nanoparticles with Heavy Metal Ions: A New Strategy for Probe Design. , 2016, Analytical chemistry.

[31]  N. Prabhakar,et al.  Ratiometric Sensing and Imaging of Intracellular pH Using Polyethylenimine-Coated Photon Upconversion Nanoprobes. , 2017, Analytical chemistry.

[32]  C. Mirkin,et al.  Upconversion Nanoprobes for the Ratiometric Luminescent Sensing of Nitric Oxide. , 2017, Journal of the American Chemical Society.

[33]  Fei Wu,et al.  Phenothiazine-cyanine-functionalized upconversion nanoparticles for LRET and colorimetric sensing of cyanide ions in water samples , 2016 .

[34]  Wei Feng,et al.  Upconversion luminescent materials: advances and applications. , 2015, Chemical reviews.

[35]  C. L. Teoh,et al.  High-efficiency in vitro and in vivo detection of Zn2+ by dye-assembled upconversion nanoparticles. , 2015, Journal of the American Chemical Society.

[36]  Guanying Chen,et al.  Ultrasmall monodisperse NaYF(4):Yb(3+)/Tm(3+) nanocrystals with enhanced near-infrared to near-infrared upconversion photoluminescence. , 2010, ACS nano.

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

[38]  Baojiu Chen,et al.  Remarkable fluorescence enhancement of upconversion composite film and its application on mercury sensing , 2017 .

[39]  Wei Feng,et al.  An Nd³⁺-sensitized upconversion nanophosphor modified with a cyanine dye for the ratiometric upconversion luminescence bioimaging of hypochlorite. , 2015, Nanoscale.

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

[41]  Lin Liu,et al.  Low temperature deformation behavior of an electromagnetically bulged 5052 aluminum alloy , 2016, Scientific Reports.

[42]  Shuyan Song,et al.  A long-wave optical pH sensor based on red upconversion luminescence of NaGdF4 nanotubes , 2014 .

[43]  Lina Zhao,et al.  Biocompatible and flexible graphene oxide/upconversion nanoparticle hybrid film for optical pH sensing. , 2014, Physical chemistry chemical physics : PCCP.

[44]  Liyi Shi,et al.  Rhodamine-modified upconversion nanoprobe for distinguishing Cu2+ from Hg2+ and live cell imaging , 2016 .

[45]  J. DesJardins,et al.  Development of Luminescent pH Sensor Films for Monitoring Bacterial Growth Through Tissue , 2014, Advanced healthcare materials.

[46]  Juyoung Yoon,et al.  Recent progress in the development of fluorescent, luminescent and colorimetric probes for detection of reactive oxygen and nitrogen species. , 2016, Chemical Society reviews.

[47]  Liming Zhang,et al.  Ratiometric fluorescent nanosensors for selective detecting cysteine with upconversion luminescence. , 2016, Biosensors & bioelectronics.

[48]  M. J. Suscavage,et al.  Efficient frequency upconversion of Tm3+ ions in Yb3+ doped barium‐thorium fluoride glass , 1988 .

[49]  Hongwei Song,et al.  A novel upconversion, fluorescence resonance energy transfer biosensor (FRET) for sensitive detection of lead ions in human serum. , 2014, Nanoscale.

[50]  Bin Li,et al.  Assembling of a functional cyclodextrin-decorated upconversion luminescence nanoplatform for cysteine-sensing. , 2015, Chemical communications.

[51]  Wei Feng,et al.  Upconversion‐Nanophosphor‐Based Functional Nanocomposites , 2013, Advanced materials.

[52]  Flora L Thorp-Greenwood,et al.  Application of d6 transition metal complexes in fluorescence cell imaging. , 2010, Chemical communications.

[53]  Yan Liu,et al.  Development of an Inner Filter Effects-Based Upconversion Nanoparticles-Curcumin Nanosystem for the Sensitive Sensing of Fluoride Ion. , 2017, ACS applied materials & interfaces.

[54]  S. Yao,et al.  Sensitive fluorescent detection of H2O2 and glucose in human serum based on inner filter effect of squaric acid-iron(III) on the fluorescence of upconversion nanoparticle. , 2017, Talanta.

[55]  Fuyou Li,et al.  Cationic iridium(III) complexes for phosphorescence staining in the cytoplasm of living cells. , 2008, Chemical communications.

[56]  D. Xing,et al.  Theranostic Upconversion Nanobeacons for Tumor mRNA Ratiometric Fluorescence Detection and Imaging-Monitored Drug Delivery. , 2016, Small.

[57]  S. Yao,et al.  Glutathione regulation-based dual-functional upconversion sensing-platform for acetylcholinesterase activity and cadmium ions. , 2017, Biosensors & bioelectronics.

[58]  Xuehua Yin,et al.  Dye-assembled nanocomposites for rapid upconversion luminescence sensing of Cu2+ , 2017 .

[59]  Qichun Zhang,et al.  Thiazole derivative-modified upconversion nanoparticles for Hg(2+) detection in living cells. , 2016, Nanoscale.

[60]  D. Zhao,et al.  Near-Infrared-Activated Upconversion Nanoprobes for Sensitive Endogenous Zn2+ Detection and Selective On-Demand Photodynamic Therapy. , 2017, Analytical chemistry.

[61]  K. Y. Zhang,et al.  A Phosphorescent Iridium(III) Complex‐Modified Nanoprobe for Hypoxia Bioimaging Via Time‐Resolved Luminescence Microscopy , 2015, Advanced science.

[62]  R. Yu,et al.  DNA-functionalized upconversion nanoparticles as biosensors for rapid, sensitive, and selective detection of Hg(2+) in complex matrices. , 2015, The Analyst.

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

[64]  Fan Zhang,et al.  Bioapplications and biotechnologies of upconversion nanoparticle-based nanosensors. , 2016, The Analyst.

[65]  Jinliang Liu,et al.  Recent Progress of Rare‐Earth Doped Upconversion Nanoparticles: Synthesis, Optimization, and Applications , 2019, Advanced science.

[66]  Hua Zhang,et al.  A cyanine-modified upconversion nanoprobe for NIR-excited imaging of endogenous hydrogen peroxide signaling in vivo. , 2015, Biomaterials.

[67]  P. Choyke,et al.  New strategies for fluorescent probe design in medical diagnostic imaging. , 2010, Chemical reviews.

[68]  Cuiling Zhang,et al.  Label-free upconversion nanoparticles-based fluorescent probes for sequential sensing of Cu2+, pyrophosphate and alkaline phosphatase activity. , 2017, Biosensors & bioelectronics.

[69]  T. Tullius,et al.  DNA strand breaking by the hydroxyl radical is governed by the accessible surface areas of the hydrogen atoms of the DNA backbone. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[70]  Zhihong Liu,et al.  A Rationally Designed Upconversion Nanoprobe for in Vivo Detection of Hydroxyl Radical. , 2015, Journal of the American Chemical Society.

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

[72]  G. Xu The covalent combination of rare earth up-conversion nanorods and a rhodamine derivative: An “off–on” Hg(II) sensing system with high selectivity , 2014 .

[73]  R. Pal,et al.  Cell-penetrating metal complex optical probes: targeted and responsive systems based on lanthanide luminescence. , 2009, Accounts of chemical research.

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

[75]  Ru-Qin Yu,et al.  MnO2-Nanosheet-Modified Upconversion Nanosystem for Sensitive Turn-On Fluorescence Detection of H2O2 and Glucose in Blood. , 2015, ACS applied materials & interfaces.

[76]  X. Qu,et al.  Upconversion nanoprobes for efficiently in vitro imaging reactive oxygen species and in vivo diagnosing rheumatoid arthritis. , 2015, Biomaterials.

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

[78]  Yingying Su,et al.  An upconversion fluorescence based turn-on probe for detecting lead(II) ions , 2014 .

[79]  C. L. Teoh,et al.  Development of a Highly Selective, Sensitive, and Fast Response Upconversion Luminescent Platform for Hydrogen Sulfide Detection , 2016 .

[80]  Zhaopeng Chen,et al.  Highly sensitive label-free colorimetric sensing of nitrite based on etching of gold nanorods. , 2012, The Analyst.

[81]  Qiang Zhao,et al.  Phosphorescent heavy-metal complexes for bioimaging. , 2011, Chemical Society reviews.

[82]  Wei Feng,et al.  A cyanine-modified nanosystem for in vivo upconversion luminescence bioimaging of methylmercury. , 2013, Journal of the American Chemical Society.

[83]  En Ma,et al.  Amine-functionalized lanthanide-doped zirconia nanoparticles: optical spectroscopy, time-resolved fluorescence resonance energy transfer biodetection, and targeted imaging. , 2012, Journal of the American Chemical Society.

[84]  Wei Huang,et al.  Inorganic-organic hybrid nanoprobe for NIR-excited imaging of hydrogen sulfide in cell cultures and inflammation in a mouse model. , 2014, Small.

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

[86]  Zhihong Liu,et al.  Construction of LRET-based nanoprobe using upconversion nanoparticles with confined emitters and bared surface as luminophore. , 2015, Journal of the American Chemical Society.

[87]  B. Cho,et al.  Two-photon probes for intracellular free metal ions, acidic vesicles, and lipid rafts in live tissues. , 2009, Accounts of chemical research.

[88]  M. Cecchini,et al.  Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease , 2016, Scientific Reports.

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

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

[91]  Fuyou Li,et al.  Phosphorescent chemosensors based on heavy-metal complexes. , 2010, Chemical Society reviews.

[92]  H. Tian,et al.  Near-IR core-substituted naphthalenediimide fluorescent chemosensors for zinc ions: ligand effects on PET and ICT channels. , 2010, Chemistry.

[93]  Lun Wang,et al.  A near-infrared luminescent Mn2+-doped NaYF4:Yb,Tm/Fe3+ upconversion nanoparticles redox reaction system for the detection of GSH/Cys/AA. , 2017, Talanta.

[94]  Yongbo Wang,et al.  Upconversion luminescence nanoprobe based on luminescence resonance energy transfer from NaYF4:Yb, Tm to Ag nanodisks , 2016 .

[95]  G. Somesfalean,et al.  Ultraviolet upconversion fluorescence in rare-earth-ion-doped Y2O3 induced by infrared diode laser excitation. , 2007, Optics letters.

[96]  Changlong Jiang,et al.  Upconversion color tuning in Ce(3+)-doped LiYF(4):Yb(3+)/Ho(3+)@LiYF(4) nanoparticles towards ratiometric fluorescence detection of chromium(III). , 2017, Journal of colloid and interface science.

[97]  K. Y. Zhang,et al.  Development of upconversion luminescent probe for ratiometric sensing and bioimaging of hydrogen sulfide. , 2014, ACS applied materials & interfaces.

[98]  Kun Zhang,et al.  Preparation, characterization and Hg(II)-sensing behavior of an up-conversion nanocomposite grafted by a rhodamine derived probe: a potential application for eco-industrial park. , 2014, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[99]  Marc Vendrell,et al.  Intracellular glutathione detection using MnO(2)-nanosheet-modified upconversion nanoparticles. , 2011, Journal of the American Chemical Society.

[100]  H. Tanke,et al.  Detection of cell and tissue surface antigens using up-converting phosphors: a new reporter technology. , 1999, Analytical biochemistry.

[101]  Y. Liu,et al.  Ultrasensitive nanosensors based on upconversion nanoparticles for selective hypoxia imaging in vivo upon near-infrared excitation. , 2014, Journal of the American Chemical Society.

[102]  Taeghwan Hyeon,et al.  Upconverting nanoparticles: a versatile platform for wide-field two-photon microscopy and multi-modal in vivo imaging. , 2015, Chemical Society reviews.

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

[104]  Xiaogang Liu,et al.  Enhancing luminescence in lanthanide-doped upconversion nanoparticles. , 2014, Angewandte Chemie.

[105]  Shuyan Song,et al.  Pure and intense orange upconversion luminescence of Eu3+ from the sensitization of Yb3+–Mn2+ dimer in NaY(Lu)F4 nanocrystals , 2014 .

[106]  Ru‐Shi Liu,et al.  The effect of surface coating on energy migration-mediated upconversion. , 2012, Journal of the American Chemical Society.

[107]  Liyi Shi,et al.  Nile Red Derivative-Modified Nanostructure for Upconversion Luminescence Sensing and Intracellular Detection of Fe(3+) and MR Imaging. , 2016, ACS applied materials & interfaces.

[108]  R. Strongin,et al.  Homocystamides promote free-radical and oxidative damage to proteins , 2009, Proceedings of the National Academy of Sciences.

[109]  Liyi Shi,et al.  Simultaneous realization of Hg(2+) sensing, magnetic resonance imaging and upconversion luminescence in vitro and in vivo bioimaging based on hollow mesoporous silica coated UCNPs and ruthenium complex. , 2015, Nanoscale.

[110]  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.

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

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

[113]  Tero Soukka,et al.  Background-free referenced luminescence sensing and imaging of pH using upconverting phosphors and color camera read-out. , 2014, Analytical chemistry.

[114]  Cid B. de Araújo,et al.  Frequency up-conversion in a borate glass doped with Pr3+ , 1988 .

[115]  Juan Tang,et al.  Simultaneous detection of hydrogen peroxide and glucose in human serum with upconversion luminescence. , 2015, Biosensors & bioelectronics.

[116]  Liyi Shi,et al.  Luminescent nanoprobes based on upconversion nanoparticles and single-walled carbon nanohorns or graphene oxide for detection of Pb2+ ion , 2016 .

[117]  Tao Yi,et al.  Up-conversion luminescent switch based on photochromic diarylethene and rare-earth nanophosphors. , 2008, Chemical communications.

[118]  S. Son,et al.  Fabrication of Magnetic Upconversion Nanohybrid for Luminescent Resonance Energy Transfer-Based Detection of Glutathione. , 2015, Journal of nanoscience and nanotechnology.

[119]  Qingsong Mei,et al.  Zinc-Dithizone Complex Engineered Upconverting Nanosensors for the Detection of Hypochlorite in Living Cells. , 2015, Small.

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

[121]  Juyoung Yoon,et al.  Fluorescent and luminescent probes for detection of reactive oxygen and nitrogen species. , 2011, Chemical Society reviews.

[122]  C. Choy,et al.  Dielectric properties and abnormal C-V characteristics of Ba[sub 0.5]Sr[sub 0.5]TiO₃-Bi[sub 1.5]ZnNb[sub 1.5]O[sub 7] composite thin films grown on MgO (001) substrates by pulsed laser deposition , 2006 .

[123]  D. Zhao,et al.  Lab on upconversion nanoparticles: optical properties and applications engineering via designed nanostructure. , 2015, Chemical Society reviews.

[124]  R. Yu,et al.  Quench-Shield Ratiometric Upconversion Luminescence Nanoplatform for Biosensing. , 2016, Analytical chemistry.