Transport of NaYF4:Er3+, Yb3+ up-converting nanoparticles into HeLa cells

An effective, simple and practically useful method to incorporate fluorescent nanoparticles inside live biological cells was developed. The internalization time and concentration dependence of a frequently used liposomal transfection factor (Lipofectamine 2000) was studied. A user friendly, one-step technique to obtain water and organic solvent soluble Er(3+) and Yb(3+) doped NaYF4 nanoparticles coated with polyvinylpyrrolidone was obtained. Structural analysis of the nanoparticles confirmed the formation of nanocrystals of the desired sizes and spectral properties. The internalization of NaYF4 nanoparticles in HeLa cervical cancer cells was determined at different nanoparticle concentrations and for incubation periods from 3 to 24 h. The images revealed a redistribution of nanoparticles inside the cell, which increases with incubation time and concentration levels, and depends on the presence of the transfection factor. The study identifies, for the first time, factors responsible for an effective endocytosis of the up-converting nanoparticles to HeLa cells. Thus, the method could be applied to investigate a wide range of future 'smart' theranostic agents. Nanoparticles incorporated into the liposomes appear to be very promising fluorescent probes for imaging real-time cellular dynamics.

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

[2]  Francisco Sanz-Rodríguez,et al.  Intracellular imaging of HeLa cells by non-functionalized NaYF4 : Er3+, Yb3+ upconverting nanoparticles. , 2010, Nanoscale.

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

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

[5]  M. Haase,et al.  Visible light emission upon near-infrared excitation in a transparent solution of nanocrystalline β-NaGdF4: Yb3+, Er3+ , 2005 .

[6]  Jungkyun Im,et al.  Cellular Uptake Properties of the Complex Derived from Quantum Dots and G8 Molecular Transporter , 2011 .

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

[8]  W. Webb,et al.  Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo , 2003, Science.

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

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

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

[12]  D. Avnir,et al.  Submicron Silica/Polystyrene Composite Particles Prepared by a One-Step Sol−Gel Process , 2003 .

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

[14]  A. Alivisatos Semiconductor Clusters, Nanocrystals, and Quantum Dots , 1996, Science.

[15]  William S Ryu,et al.  Upconverting nanophosphors for bioimaging , 2009, Nanotechnology.

[16]  Vasilis Ntziachristos,et al.  Looking and listening to light: the evolution of whole-body photonic imaging , 2005, Nature Biotechnology.

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

[18]  Nancy A Monteiro-Riviere,et al.  Mechanisms of quantum dot nanoparticle cellular uptake. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[19]  Chun-Hua Yan,et al.  Self-organized monolayer of nanosized ceria colloids stabilized by poly(vinylpyrrolidone). , 2006, The journal of physical chemistry. B.

[20]  Yongzhuo Li,et al.  Synthesis and Upconversion Luminescence of Hexagonal‐Phase NaYF4:Yb, Er3+ Phosphors of Controlled Size and Morphology , 2005 .

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

[22]  Sava Sakadžić,et al.  Dendritic upconverting nanoparticles enable in vivo multiphoton microscopy with low-power continuous wave sources , 2012, Proceedings of the National Academy of Sciences.

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

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

[25]  D. Piston Imaging living cells and tissues by two-photon excitation microscopy. , 1999, Trends in cell biology.

[26]  J. L. Schlenker,et al.  Computed X-ray Powder Diffraction Patterns for Ultrasmall Zeolite Crystals , 1996 .

[27]  Wenjun Yang,et al.  Synthesis, Characterization, and Biological Application of Size-Controlled Nanocrystalline NaYF4:Yb,Er Infrared-to-Visible Up-Conversion Phosphors , 2004 .

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

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

[30]  Tero Soukka,et al.  Simultaneous use of time-resolved fluorescence and anti-stokes photoluminescence in a bioaffinity assay. , 2005, Analytical chemistry.

[31]  F. Zhang,et al.  Cerium oxide nanoparticles: Size-selective formation and structure analysis , 2002 .

[32]  L. Ye,et al.  Biocompatibility Study of PEI-NaYF4: Yb,Er Upconversion Nanoparticles , 2008 .

[33]  K. Krämer,et al.  Novel materials doped with trivalent lanthanides and transition metal ions showing near-infrared to visible photon upconversion , 2005 .

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

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

[36]  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.

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

[38]  J. Mu,et al.  A gold nanocomposite made soluble in both water and oil by the addition of a second adsorption layer of poly-N-vinyl-2-pyrrolidone on gold nanoparticles that have been made hydrophobic , 2006 .

[39]  Eva M Sevick-Muraca,et al.  Fluorescence-enhanced, near infrared diagnostic imaging with contrast agents. , 2002, Current opinion in chemical biology.

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

[41]  H. Tanke,et al.  Infrared up-converting phosphors for bioassays. , 2005, IEE proceedings. Nanobiotechnology.

[42]  Juan Rodríguez-Carvajal,et al.  Recent advances in magnetic structure determination by neutron powder diffraction , 1993 .

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

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

[45]  Chii-Wann Lin,et al.  Surface plasmon effects on two photon luminescence of gold nanorods. , 2009, Optics express.

[46]  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.

[47]  †. A. Tao Li,et al.  Luminescence of Europium(III) and Terbium(III) Complexes Incorporated in Poly(Vinyl Pyrrolidone) Matrix , 2001 .

[48]  W. Webb,et al.  Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[49]  P. Couvreur,et al.  Nanoparticles in cancer therapy and diagnosis. , 2002, Advanced drug delivery reviews.