High-resolution light microscopy using luminescent nanoparticles.

This review presents recent progress in the development of the luminescent nanoparticles for confocal and multiphoton microscopy. Four classes of nanomaterials are discussed: (1) silica-based nanoparticles doped with fluorescent molecules, (2) gold nanoparticles, (3) semiconductor nanocrystals (quantum dots/rods), and (4) nanophosphors. Special considerations are given to recently developed imaging nanoprobes, such as (1) organically modified silica (ORMOSIL) nanoparticles doped with two-photon absorbing fluorophores, which exhibit aggregation-enhanced fluorescence (AEF), and (2) nanophosphors (ceramic nanoparticles containing luminescent lanthanoid ions). Advantages and disadvantages of every class of nanomaterials and their specific applications are briefly discussed.

[1]  P. Prasad,et al.  Aggregation‐Enhanced Fluorescence and Two‐Photon Absorption in Nanoaggregates of a 9,10‐Bis[4′‐(4″‐aminostyryl)styryl]anthracene Derivative , 2006 .

[2]  Alaaldin M. Alkilany,et al.  Gold nanoparticles in biology: beyond toxicity to cellular imaging. , 2008, Accounts of chemical research.

[3]  W. Webb,et al.  Nonlinear magic: multiphoton microscopy in the biosciences , 2003, Nature Biotechnology.

[4]  Ji-Xin Cheng,et al.  Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects † , 2009, Photochemistry and photobiology.

[5]  Kazuya Kikuchi,et al.  Time-resolved long-lived luminescence imaging method employing luminescent lanthanide probes with a new microscopy system. , 2007, Journal of the American Chemical Society.

[6]  Hiromi Okamoto,et al.  Photoluminescence from gold nanoplates induced by near-field two-photon absorption , 2006 .

[7]  M. V. Kanzyuba,et al.  Nanodiamond Photoemitters Based on Strong Narrow‐Band Luminescence from Silicon‐Vacancy Defects , 2009 .

[8]  Philip S Low,et al.  In vitro and in vivo two-photon luminescence imaging of single gold nanorods. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. Chu,et al.  Effects of the S ∕ Zn Ratio on the Photoluminescence Properties of Color-Tunable ZnS:Mn Nanophosphors , 2009 .

[10]  M. Haase,et al.  Lanthanide-Doped NaYF4 Nanocrystals in Aqueous Solution Displaying Strong Up-Conversion Emission , 2007 .

[11]  Sang-Don Jung,et al.  Enhanced emission and its switching in fluorescent organic nanoparticles. , 2002, Journal of the American Chemical Society.

[12]  Chih-Wei Lai,et al.  The empirical correlation between size and two-photon absorption cross section of CdSe and CdTe quantum dots. , 2006, Small.

[13]  Fiorenzo Vetrone,et al.  Synthesis of colloidal upconverting NaYF4 nanocrystals doped with Er3+, Yb3+ and Tm3+, Yb3+ via thermal decomposition of lanthanide trifluoroacetate precursors. , 2006, Journal of the American Chemical Society.

[14]  Kemin Wang,et al.  Bionanotechnology based on silica nanoparticles , 2004, Medicinal research reviews.

[15]  Christine A Iacobuzio-Donahue,et al.  Claudin 4 protein expression in primary and metastatic pancreatic cancer: support for use as a therapeutic target. , 2004, American journal of clinical pathology.

[16]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[17]  Ji-Xin Cheng,et al.  Gold Nanorods Mediate Tumor Cell Death by Compromising Membrane Integrity , 2007, Advanced materials.

[18]  Ji-Xin Cheng,et al.  Hyperthermic effects of gold nanorods on tumor cells. , 2007, Nanomedicine.

[19]  Yan Zhang,et al.  Protease-modulated cellular uptake of quantum dots. , 2006, Nano letters.

[20]  P. Prasad,et al.  Cellular Signaling and Protein−Protein Interactions Studied Using Fluorescence Recovery after Photobleaching† , 2004 .

[21]  T. Isobe,et al.  Wet chemical synthesis and photoluminescence properties of YVO4:Bi3+,Eu3+ nanophosphors , 2008 .

[22]  E. Neher,et al.  Highly nonlinear photodamage in two-photon fluorescence microscopy. , 2001, Biophysical journal.

[23]  P. Prasad,et al.  Intraparticle energy transfer and fluorescence photoconversion in nanoparticles : An optical highlighter nanoprobe for two-photon bioimaging , 2007 .

[24]  Chung‐Hsin Lu,et al.  Photoluminescence Characteristics of $Y_2O_3 : Eu^{3+}$ Nanophosphors Prepared Using Sol-Gel Thermolysis , 2001 .

[25]  Weiming Liu,et al.  In vitro cancer cell imaging and therapy using transferrin-conjugated gold nanoparticles. , 2009, Cancer letters.

[26]  P. Alivisatos The use of nanocrystals in biological detection , 2004, Nature Biotechnology.

[27]  Watt W Webb,et al.  Blinking and nonradiant dark fraction of water-soluble quantum dots in aqueous solution. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Maggini,et al.  Cell penetrating silica nanoparticles doped with two-photon absorbing fluorophores , 2006 .

[29]  Qi Zhou,et al.  Tumor-targeting nanoimmunoliposome complex for short interfering RNA delivery. , 2005, Human gene therapy.

[30]  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.

[31]  Hassan S. Bazzi,et al.  Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots , 2005, Journal of Molecular Medicine.

[32]  A. Estrada,et al.  Two-photon-induced photoluminescence imaging of tumors using near-infrared excited gold nanoshells , 2008, 2008 Conference on Lasers and Electro-Optics and 2008 Conference on Quantum Electronics and Laser Science.

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

[34]  T. Krauss,et al.  Flow cytometric analysis to detect pathogens in bacterial cell mixtures using semiconductor quantum dots. , 2008, Analytical chemistry.

[35]  Judith Grimm,et al.  Highly efficient near-infrared to visible up-conversion process in NaYF4:Er3+,Yb3+ , 2005 .

[36]  Kemin Wang,et al.  Uptake of silica-coated nanoparticles by HeLa cells. , 2005, Journal of nanoscience and nanotechnology.

[37]  Zeev Rosenzweig,et al.  Synthesis and application of quantum dots FRET-based protease sensors. , 2006, Journal of the American Chemical Society.

[38]  S. Nie,et al.  Luminescent quantum dots for multiplexed biological detection and imaging. , 2002, Current opinion in biotechnology.

[39]  Moungi G Bawendi,et al.  Compact biocompatible quantum dots functionalized for cellular imaging. , 2008, Journal of the American Chemical Society.

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

[41]  Rakesh K. Sharma,et al.  Surface modified ormosil nanoparticles. , 2004, Journal of colloid and interface science.

[42]  Hong Ding,et al.  Imaging pancreatic cancer using bioconjugated InP quantum dots. , 2009, ACS nano.

[43]  Sailing He,et al.  Imaging pancreatic cancer using surface-functionalized quantum dots. , 2007, The journal of physical chemistry. B.

[44]  Masato Yasuhara,et al.  Physicochemical Properties and Cellular Toxicity of Nanocrystal Quantum Dots Depend on Their Surface Modification , 2004 .

[45]  Rafael Yuste,et al.  Fluorescence microscopy today , 2005, Nature Methods.

[46]  Indrajit Roy,et al.  Ceramic-based nanoparticles entrapping water-insoluble photosensitizing anticancer drugs: a novel drug-carrier system for photodynamic therapy. , 2003, Journal of the American Chemical Society.

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

[48]  Paras N Prasad,et al.  Organically modified silica nanoparticles co-encapsulating photosensitizing drug and aggregation-enhanced two-photon absorbing fluorescent dye aggregates for two-photon photodynamic therapy. , 2007, Journal of the American Chemical Society.

[49]  Mizuo Maeda,et al.  Improvement of dispersion stability and characterization of upconversion nanophosphors covalently modified with PEG as a fluorescence bioimaging probe , 2008, Journal of Materials Science.

[50]  G. J. Brakenhoff,et al.  Confocal scanning light microscopy with high aperture immersion lenses , 1979 .

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

[52]  Xiaobo Chen,et al.  Semiconductor quantum dots for photodynamic therapy. , 2003, Journal of the American Chemical Society.

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

[54]  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 .

[55]  Xueyuan Chen,et al.  Energy levels and optical spectroscopy of Er3+ in Gd2O3 nanocrystals , 2007 .

[56]  Uri Banin,et al.  Fluorescence quantum yield of CdSe/ZnS nanocrystals investigated by correlated atomic-force and single-particle fluorescence microscopy , 2002 .

[57]  Sung Ju Cho,et al.  Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. , 2005, Chemistry & biology.

[58]  M. El-Sayed Spectroscopic determination of the melting energy of a gold nanorod , 2001 .

[59]  Xun Wang,et al.  Branched NaYF(4) nanocrystals with luminescent properties. , 2007, Inorganic chemistry.

[60]  Sarah M. Buck,et al.  Nanoscale probes encapsulated by biologically localized embedding (PEBBLEs) for ion sensing and imaging in live cells. , 2004, Talanta: The International Journal of Pure and Applied Analytical Chemistry.

[61]  Wen-Hsiung Chan,et al.  CdSe quantum dots induce apoptosis in human neuroblastoma cells via mitochondrial-dependent pathways and inhibition of survival signals. , 2006, Toxicology letters.

[62]  Weihong Tan,et al.  TAT conjugated, FITC doped silica nanoparticles for bioimaging applications. , 2004, Chemical communications.

[63]  Ya‐Ping Sun,et al.  Carbon dots for multiphoton bioimaging. , 2007, Journal of the American Chemical Society.

[64]  Paras N Prasad,et al.  Folate-receptor-mediated delivery of InP quantum dots for bioimaging using confocal and two-photon microscopy. , 2005, Journal of the American Chemical Society.

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

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

[67]  Tim Liedl,et al.  Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. , 2005, Nano letters.

[68]  J. Lichtman,et al.  Optical sectioning microscopy , 2005, Nature Methods.

[69]  J. Nadeau,et al.  FRET between CdSe quantum dots in lipid vesicles and water- and lipid-soluble dyes , 2004 .

[70]  Dongqing Wu,et al.  An aqueous route to multicolor photoluminescent carbon dots using silica spheres as carriers. , 2009, Angewandte Chemie.

[71]  Xiaogang Liu,et al.  Upconversion multicolor fine-tuning: visible to near-infrared emission from lanthanide-doped NaYF4 nanoparticles. , 2008, Journal of the American Chemical Society.

[72]  Ken-Tye Yong,et al.  Biocompatible luminescent silicon quantum dots for imaging of cancer cells. , 2008, ACS nano.

[73]  Scott C. Brown,et al.  Nanoparticles for bioimaging. , 2006, Advances in colloid and interface science.

[74]  Markus P. Hehlen,et al.  Hexagonal Sodium Yttrium Fluoride Based Green and Blue Emitting Upconversion Phosphors , 2004 .

[75]  Sailing He,et al.  Quantum rod bioconjugates as targeted probes for confocal and two-photon fluorescence imaging of cancer cells. , 2007, Nano letters.

[76]  Kemin Wang,et al.  A novel fluorescent label based on organic dye-doped silica nanoparticles for HepG liver cancer cell recognition. , 2004, Journal of nanoscience and nanotechnology.

[77]  K. Sokolov,et al.  Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods. , 2007, Nano letters.

[78]  Indrajit Roy,et al.  Covalently dye-linked, surface-controlled, and bioconjugated organically modified silica nanoparticles as targeted probes for optical imaging. , 2008, ACS nano.

[79]  Tymish Y. Ohulchanskyy,et al.  Optical tracking of organically modified silica nanoparticles as DNA carriers: a nonviral, nanomedicine approach for gene delivery. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[80]  Raheela Ashfaq,et al.  Claudin 4 Protein Expression in Primary and Metastatic Pancreatic Cancer , 2004 .

[81]  T. Mihaljevic,et al.  Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping , 2004, Nature Biotechnology.

[82]  K. König,et al.  Multiphoton microscopy in life sciences , 2000, Journal of microscopy.

[83]  S. Pathak,et al.  Hydroxylated quantum dots as luminescent probes for in situ hybridization. , 2001, Journal of the American Chemical Society.

[84]  U. Banin,et al.  Synthesis and Properties of CdSe/ZnS Core/Shell Nanorods , 2003 .

[85]  I. Sokolov,et al.  Novel fluorescent silica nanoparticles: towards ultrabright silica nanoparticles. , 2008, Small.

[86]  Prem Gurnani,et al.  Pegylated, steptavidin-conjugated quantum dots are effective detection elements for reverse-phase protein microarrays. , 2005, Bioconjugate chemistry.

[87]  Warren C. W. Chan,et al.  Quantum Dots in Biological and Biomedical Research: Recent Progress and Present Challenges , 2006 .

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

[89]  Harish Chander,et al.  Development of nanophosphors—A review , 2005 .

[90]  Indrajit Roy,et al.  Organically modified silica nanoparticles with covalently incorporated photosensitizer for photodynamic therapy of cancer. , 2007, Nano letters.

[91]  G. Patterson,et al.  Photobleaching in two-photon excitation microscopy. , 2000, Biophysical journal.

[92]  Y. Gogotsi,et al.  Wet chemistry route to hydrophobic blue fluorescent nanodiamond. , 2009, Journal of the American Chemical Society.

[93]  Hong Yang,et al.  High‐Brightness LaPO4:Ce3+, Tb3+ Nanophosphors: Reductive Hydrothermal Synthesis and Photoluminescent Properties , 2008 .

[94]  Ya-Wen Zhang,et al.  Single-crystalline and monodisperse LaF3 triangular nanoplates from a single-source precursor. , 2005, Journal of the American Chemical Society.

[95]  Gang Chen,et al.  Enhanced multiphoton ultraviolet and blue upconversion emissions in Y 2O3 : Er3+ nanocrystals by codoping with Li+ ions , 2008 .

[96]  Weiwei Guo,et al.  Anticancer drug-DNA interactions measured using a photoinduced electron-transfer mechanism based on luminescent quantum dots. , 2009, Analytical chemistry.

[97]  Weihong Tan,et al.  FloDots: luminescent nanoparticles , 2006, Analytical and bioanalytical chemistry.

[98]  P. Prasad,et al.  Silica nanobubbles containing an organic dye in a multilayered organic/inorganic heterostructure with enhanced luminescence , 2000 .

[99]  Adela C. Bonoiu,et al.  Aggregation‐Enhanced Fluorescence in Organically Modified Silica Nanoparticles: A Novel Approach toward High‐Signal‐Output Nanoprobes for Two‐Photon Fluorescence Bioimaging , 2007 .

[100]  V. P. N. Nampoori,et al.  Measurement of the absolute fluorescence quantum yield of rhodamine B solution using a dual-beam thermal lens technique , 1996 .

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

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

[103]  J. Vela,et al.  "Giant" multishell CdSe nanocrystal quantum dots with suppressed blinking. , 2008, Journal of the American Chemical Society.

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

[105]  Shuming Nie,et al.  Engineering Luminescent Quantum Dots for In Vivo Molecular and Cellular Imaging , 2006, Annals of Biomedical Engineering.

[106]  R. Langer,et al.  Intracellular delivery of core-shell fluorescent silica nanoparticles. , 2008, Biomaterials.

[107]  Shraboni Das,et al.  Inorganic-organic hybrid nanoparticles from n-octyl triethoxy silane. , 2002, Journal of colloid and interface science.

[108]  P. Prasad,et al.  Multi-photon excitation properties of CdSe quantum dots solutions and optical limiting behavior in infrared range. , 2007, Optics express.

[109]  H S Kwok,et al.  Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. , 2001, Chemical communications.