Multimodal-luminescence core-shell nanocomposites for targeted imaging of tumor cells.

Uniform silica-coated NaYF(4): 20 mol % Yb, 2 mol % Er nanocomposites with good dispersibility, containing organic dye incorporated in the silica shell and folic acid conjugated on the surface of the shell, were prepared and characterized. The core-shell nanocomposites are 20-22 nm in size, water soluble, and buffer stable, with good photostability and biocompatibility. Folic acid (FA) offers a means of targeting human cells that greatly overexpress the folate receptor (FR). By the use of confocal microscopy and quantitative flow cytometry analysis, we demonstrate the receptor-mediated delivery of FA-conjugated nanocomposites targeting FR-positive cell lines, such as KB cells. The receptor-mediated targeting was confirmed by a comparison with the uptake of these nanocomposites in FR-negative cell lines, such as MCF-7. These results show that the silica-coated upconverting nanophosphor (UCNP) nanocomposites prepared by our strategy can potentially be useful as multimodal bioimaging agents.

[1]  Alfons van Blaaderen,et al.  Dispersions of Rhodamine-Labeled Silica Spheres: Synthesis, Characterization, and Fluorescence Confocal Scanning Laser Microscopy , 1994 .

[2]  N. Jana,et al.  Preparation of Polystyrene- and Silica-Coated Gold Nanorods and Their Use as Templates for the Synthesis of Hollow Nanotubes , 2001 .

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

[4]  Thomas Nann,et al.  A four-color colloidal multiplexing nanoparticle system. , 2008, ACS nano.

[5]  P. Low,et al.  Folate-mediated targeting: from diagnostics to drug and gene delivery. , 2001, Drug discovery today.

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

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

[8]  Horst Weller,et al.  Biofunctionalization of Silica-Coated CdTe and Gold Nanocrystals , 2002 .

[9]  Thomas Nann,et al.  Einzelne Quantenpunkte in Siliciumdioxid‐Kugeln , 2004 .

[10]  G. Ederer,et al.  Rapid Hippurate Hydrolysis Method for Presumptive Identification of Group B Streptococci , 1975, Journal of clinical microbiology.

[11]  T. Nann,et al.  Single Quantum Dots in Silica Spheres by Microemulsion Synthesis , 2005 .

[12]  Xiaogang Peng,et al.  Photochemical instability of CdSe nanocrystals coated by hydrophilic thiols. , 2001, Journal of the American Chemical Society.

[13]  F. V. van Veggel,et al.  Bright white light through up-conversion of a single NIR source from sol-gel-derived thin film made with Ln3+-doped LaF3 nanoparticles. , 2005, Journal of the American Chemical Society.

[14]  Tao Yi,et al.  A highly selective fluorescence turn-on sensor for cysteine/homocysteine and its application in bioimaging. , 2007, Journal of the American Chemical Society.

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

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

[17]  H. Dai,et al.  In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. , 2020, Nature nanotechnology.

[18]  N. Pradhan,et al.  Surface ligand dynamics in growth of nanocrystals. , 2007, Journal of the American Chemical Society.

[19]  O. Lev,et al.  Direct Synthesis and Characterization of Gold and Other Noble Metal Nanodispersions in Sol−Gel-Derived Organically Modified Silicates , 1999 .

[20]  Michael C. Wilson,et al.  Surfactant-assisted synthesis of water-soluble and biocompatible semiconductor quantum dot micelles. , 2005, Nano letters (Print).

[21]  P. Saigo,et al.  Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein. , 1993, The American journal of pathology.

[22]  C. Brinker,et al.  Synthesis of organo-silane functionalized nanocrystal micelles and their self-assembly. , 2005, Journal of the American Chemical Society.

[23]  S. Nie,et al.  Quantum dot bioconjugates for ultrasensitive nonisotopic detection. , 1998, Science.

[24]  A. Vrij,et al.  Synthesis and characterization of colloidal dispersions of fluorescent, monodisperse silica spheres , 1992 .

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

[26]  Bai Yang,et al.  Manipulation of aqueous growth of CdTe nanocrystals to fabricate colloidally stable one-dimensional nanostructures. , 2006, Journal of the American Chemical Society.

[27]  Xiaogang Peng,et al.  Alternative Routes toward High Quality CdSe Nanocrystals , 2001 .

[28]  P. Low,et al.  Folate receptor-targeted drugs for cancer and inflammatory diseases. , 2004, Advanced drug delivery reviews.

[29]  Xiaodong Chen,et al.  Lateral Patterning of Luminescent CdSe Nanocrystals by Selective Dewetting from Self-Assembled Organic Templates , 2004 .

[30]  P. Low,et al.  Selective targeting of malignant cells with cytotoxin-folate conjugates. , 1994, Journal of drug targeting.

[31]  Fuyou Li,et al.  Hydrothermal synthesis of hexagonal lanthanide-doped LaF3 nanoplates with bright upconversion luminescence , 2008, Nanotechnology.

[32]  Paul Mulvaney,et al.  Synthesis of Nanosized Gold−Silica Core−Shell Particles , 1996 .

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

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

[35]  Qing Peng,et al.  A general strategy for nanocrystal synthesis , 2005, Nature.

[36]  The biological chemistry of folate receptors. , 1992 .

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

[38]  P. Low,et al.  Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. , 2005, Analytical biochemistry.

[39]  Fuyou Li,et al.  Multisignaling optical-electrochemical sensor for Hg2+ based on a rhodamine derivative with a ferrocene unit. , 2007, Organic letters.

[40]  Timothy Thatt Yang Tan,et al.  Robust, Non‐Cytotoxic, Silica‐Coated CdSe Quantum Dots with Efficient Photoluminescence , 2005 .

[41]  Yadong Li,et al.  Controlled Synthesis and Luminescence of Lanthanide Doped NaYF4 Nanocrystals , 2007 .

[42]  Jinkyu Lee,et al.  Multifunctional nanoparticles possessing a "magnetic motor effect" for drug or gene delivery. , 2005, Angewandte Chemie.

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

[44]  Fuyou Li,et al.  Highly sensitive and fast responsive fluorescence turn-on chemodosimeter for Cu2+ and its application in live cell imaging. , 2008, Chemistry.

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

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

[47]  B. Bauer,et al.  Length‐Dependent Uptake of DNA‐Wrapped Single‐Walled Carbon Nanotubes , 2007 .

[48]  C. Bustamante,et al.  Conjugation of DNA to Silanized Colloidal Semiconductor Nanocrystalline Quantum Dots , 2002 .

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

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

[51]  R. K. Cannan,et al.  A modified photometric ninhydrin method for the analysis of amino and imino acids. , 1953, The Journal of biological chemistry.

[52]  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.

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

[54]  Jackie Y Ying,et al.  Silica-coated nanocomposites of magnetic nanoparticles and quantum dots. , 2005, Journal of the American Chemical Society.

[55]  Ya-Wen Zhang,et al.  High-quality sodium rare-earth fluoride nanocrystals: controlled synthesis and optical properties. , 2006, Journal of the American Chemical Society.

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

[57]  H. Dai,et al.  Noncovalent functionalization of carbon nanotubes by fluorescein-polyethylene glycol: supramolecular conjugates with pH-dependent absorbance and fluorescence. , 2007, Journal of the American Chemical Society.

[58]  Jung Ho Yu,et al.  Magnetic fluorescent delivery vehicle using uniform mesoporous silica spheres embedded with monodisperse magnetic and semiconductor nanocrystals. , 2006, Journal of the American Chemical Society.

[59]  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.

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

[61]  Philip S Low,et al.  Folate-mediated delivery of macromolecular anticancer therapeutic agents. , 2002, Advanced drug delivery reviews.

[62]  B. Korgel,et al.  Synthesis and magnetic properties of silica-coated FePt nanocrystals. , 2006, The journal of physical chemistry. B.

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

[64]  Philip S Low,et al.  Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. , 2008, Accounts of chemical research.

[65]  Igor L. Medintz,et al.  Quantum dot bioconjugates for imaging, labelling and sensing , 2005, Nature materials.

[66]  Zhivko Zhelev,et al.  Single quantum dot-micelles coated with silica shell as potentially non-cytotoxic fluorescent cell tracers. , 2006, Journal of the American Chemical Society.

[67]  Thomas Nann,et al.  Single quantum dots in spherical silica particles. , 2004, Angewandte Chemie.

[68]  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.

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

[70]  V. Yam,et al.  Multifunctional ruthenium(II) polypyridine complex-based core-shell magnetic silica nanocomposites: magnetism, luminescence, and electrochemiluminescence. , 2008, ACS nano.

[71]  Horst Weller,et al.  Ligand design and bioconjugation of colloidal gold nanoparticles. , 2002, Angewandte Chemie.

[72]  Yadong Li,et al.  Na(Y1.5 Na0.5)F6 single-crystal nanorods as multicolor luminescent materials. , 2006, Nano letters.

[73]  Emril Mohamed Ali,et al.  Controlled photostability of luminescent nanocrystalline ZnO solution for selective detection of aldehydes. , 2007, Chemical communications.

[74]  Timothy Thatt Yang Tan,et al.  Size control, shape evolution, and silica coating of near-infrared-emitting PbSe quantum dots , 2007 .

[75]  Vincent Noireaux,et al.  In Vivo Imaging of Quantum Dots Encapsulated in Phospholipid Micelles , 2002, Science.

[76]  P. Low,et al.  Folate targeting of haptens to cancer cell surfaces mediates immunotherapy of syngeneic murine tumors , 2002, Cancer Immunology, Immunotherapy.

[77]  H. Weller,et al.  Ligandendesign und Biokonjugation kolloidaler Gold‐Nanopartikel , 2002 .

[78]  Donghoon Lee,et al.  Optical and MRI multifunctional nanoprobe for targeting gliomas. , 2005, Nano letters.

[79]  Zhengquan Li,et al.  Monodisperse silica-coated polyvinylpyrrolidone/NaYF(4) nanocrystals with multicolor upconversion fluorescence emission. , 2006, Angewandte Chemie.

[80]  V. S. Lin,et al.  Mesoporous silica nanoparticles deliver DNA and chemicals into plants. , 2007, Nature nanotechnology.

[81]  J. Ying,et al.  Nanoparticle Architectures Templated by SiO2/Fe2O3 Nanocomposites , 2006 .

[82]  Victoria J Allan,et al.  Light Microscopy Techniques for Live Cell Imaging , 2003, Science.

[83]  B. Wilson,et al.  In Vivo Fluorescence Spectroscopy and Imaging for Oncological Applications , 1998, Photochemistry and photobiology.

[84]  Elizabeth L. Bentzen,et al.  Surface modification to reduce nonspecific binding of quantum dots in live cell assays. , 2005, Bioconjugate chemistry.