Photostimulable Near-Infrared Persistent Luminescent Nanoprobes for Ultrasensitive and Longitudinal Deep-Tissue Bio-Imaging

In vivo fluorescence imaging suffers from suboptimal signal-to-noise ratio and shallow detection depth, which is caused by the strong tissue autofluorescence under constant external excitation and the scattering and absorption of short-wavelength light in tissues. Here we address these limitations by using a novel type of optical nanoprobes, photostimulable LiGa5O8:Cr3+ near-infrared (NIR) persistent luminescence nanoparticles, which, with very-long-lasting NIR persistent luminescence and unique photo-stimulated persistent luminescence (PSPL) capability, allow optical imaging to be performed in an excitation-free and hence, autofluorescence-free manner. LiGa5O8:Cr3+ nanoparticles pre-charged by ultraviolet light can be repeatedly (>20 times) stimulated in vivo, even in deep tissues, by short-illumination (~15 seconds) with a white light-emitting-diode flashlight, giving rise to multiple NIR PSPL that expands the tracking window from several hours to more than 10 days. Our studies reveal promising potential of these nanoprobes in cell tracking and tumor targeting, exhibiting exceptional sensitivity and penetration that far exceed those afforded by conventional fluorescence imaging.

[1]  Igor L. Medintz,et al.  Materials for fluorescence resonance energy transfer analysis: beyond traditional donor-acceptor combinations. , 2006, Angewandte Chemie.

[2]  根井 充.  Current topics in ionizing radiation research , 2012 .

[3]  Zhengwei Pan,et al.  Sunlight-activated long-persistent luminescence in the near-infrared from Cr(3+)-doped zinc gallogermanates. , 2011, Nature materials.

[4]  S. J. Dhoble,et al.  Phosphate Phosphors for Solid-State Lighting , 2012 .

[5]  Nicholas J Turro,et al.  Toward the syntheses of universal ligands for metal oxide surfaces: controlling surface functionality through click chemistry. , 2007, Journal of the American Chemical Society.

[6]  Wei Feng,et al.  Upconversion luminescence imaging of cells and small animals , 2013, Nature Protocols.

[7]  Salaheddine Alahrache,et al.  Considerable Improvement of Long-Persistent Luminescence in Germanium and Tin Substituted ZnGa2O4 , 2013 .

[8]  M. Bawendi,et al.  Renal clearance of quantum dots , 2007, Nature Biotechnology.

[9]  R. Smalley,et al.  Structure-Assigned Optical Spectra of Single-Walled Carbon Nanotubes , 2002, Science.

[10]  H. Szymczak,et al.  Optical spectrum of Cr3+ in the spinel LiGa5O8 , 1975 .

[11]  Peter Choyke,et al.  Comparison of noninvasive fluorescent and bioluminescent small animal optical imaging. , 2003, BioTechniques.

[12]  M. Grätzel,et al.  Surface Modification of Titanium with Phosphonic Acid To Improve Bone Bonding: Characterization by XPS and ToF-SIMS , 2002 .

[13]  Craig H Meyer,et al.  Technology Insight: in vivo cell tracking by use of MRI , 2006, Nature Clinical Practice Cardiovascular Medicine.

[14]  Christian E Badr,et al.  Bioluminescence imaging: progress and applications. , 2011, Trends in biotechnology.

[15]  Reuven Chen,et al.  THEORY OF THERMOLUMINESCENCE AND RELATED PHENOMENA , 1997 .

[16]  Nobuyoshi Takeuchi,et al.  A New Long Phosphorescent Phosphor with High Brightness, SrAl2 O 4 : Eu2 + , Dy3 + , 1996 .

[17]  S. Sahoo,et al.  Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[18]  Bernd J. Pichler,et al.  Cell tracking with optical imaging , 2008, European Radiology.

[19]  Yan Li,et al.  In Vivo Cancer Targeting and Imaging-Guided Surgery with Near Infrared-Emitting Quantum Dot Bioconjugates , 2012, Theranostics.

[20]  Kohei Soga,et al.  Upconverting and NIR emitting rare earth based nanostructures for NIR-bioimaging. , 2013, Nanoscale.

[21]  Setsuhisa Tanabe,et al.  Tunable trap depth in Zn(Ga1−xAlx)2O4:Cr,Bi red persistent phosphors: considerations of high-temperature persistent luminescence and photostimulated persistent luminescence , 2013 .

[22]  Y. Sakka,et al.  Effect of polyethylenimine on the dispersion and electrophoretic deposition of nano-sized titania aqueous suspensions , 2006 .

[23]  R Lejeune,et al.  Chemiluminescence as diagnostic tool. A review. , 2000, Talanta.

[24]  Ismail Ab Rahman,et al.  Synthesis of silica nanoparticles by sol-gel: size-dependent properties, surface modification, and applications in silica-polymer nanocomposites — a review , 2012 .

[25]  R. Tsien,et al.  Evolution of new nonantibody proteins via iterative somatic hypermutation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Weibo Cai,et al.  Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy , 2008, Proceedings of the National Academy of Sciences.

[27]  Alessandra Ghiani,et al.  Resolution of Viable and Membrane-Compromised Bacteria in Freshwater and Marine Waters Based on Analytical Flow Cytometry and Nucleic Acid Double Staining , 2001, Applied and Environmental Microbiology.

[28]  H. Kamiya,et al.  Influence of Solid Fraction on the Optimum Molecular Weight of Polymer Dispersants in Aqueous TiO2 Nanoparticle Suspensions , 2007 .

[29]  C. Contag,et al.  Advances in in vivo bioluminescence imaging of gene expression. , 2002, Annual review of biomedical engineering.

[30]  Feng Liu,et al.  Photostimulated near-infrared persistent luminescence as a new optical read-out from Cr3+-doped LiGa5O8 , 2013, Scientific Reports.

[31]  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.

[32]  Y. Chevalier,et al.  Dispersion of hematite suspensions with sodium polymethacrylate dispersants in alkaline medium , 2006 .

[33]  Soodabeh Davaran,et al.  Quantum dots: synthesis, bioapplications, and toxicity , 2012, Nanoscale Research Letters.

[34]  P. Geladi,et al.  Large uptake of titania and iron oxide nanoparticles in the nucleus of lung epithelial cells as measured by Raman imaging and multivariate classification. , 2013, Biophysical journal.

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

[36]  Ravindran Girija Aswathy,et al.  Near-infrared quantum dots for deep tissue imaging , 2010, Analytical and bioanalytical chemistry.

[37]  Weibo Cai,et al.  Multimodality Molecular Imaging of Tumor Angiogenesis , 2008, Journal of Nuclear Medicine.

[38]  Michael Z. Lin,et al.  Mammalian Expression of Infrared Fluorescent Proteins Engineered from a Bacterial Phytochrome , 2009, Science.

[39]  J. Delhalle,et al.  Surface modification of aluminum by n-pentanephosphonic acid: XPS and electrochemical evaluation , 2003 .

[40]  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 .

[41]  John V Frangioni,et al.  Self-illuminating quantum dots light the way , 2006, Nature Biotechnology.

[42]  J. G. Solé,et al.  An Introduction to the Optical Spectroscopy of Inorganic Solids , 2005 .

[43]  David A. Cheresh,et al.  Role of integrins in cell invasion and migration , 2002, Nature Reviews Cancer.

[44]  M. Delcourt,et al.  Microaggregates of non-noble metals and bimetallic alloys prepared by radiation-induced reduction , 1985, Nature.

[45]  A. El-Sadik,et al.  Nanoparticle-labeled stem cells: a novel therapeutic vehicle , 2010, Clinical pharmacology : advances and applications.

[46]  R. Tsien,et al.  Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein , 2004, Nature Biotechnology.

[47]  S. Ferrari,et al.  ExGen 500 is an efficient vector for gene delivery to lung epithelial cells in vitro and in vivo , 1997, Gene Therapy.

[48]  B. L. O’dell,et al.  Handbook of nutritionally essential mineral elements. , 1997 .

[49]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[50]  U. Schubert,et al.  Surface Modification and Functionalization of Metal and Metal Oxide Nanoparticles by Organic Ligands , 2008 .

[51]  S. Sinha,et al.  Chromium is not an essential trace element for mammals: effects of a “low-chromium” diet , 2011, JBIC Journal of Biological Inorganic Chemistry.

[52]  S. Schweizer.  Physics and current understanding of X-ray storage phosphors , 2001 .

[53]  Sanjiv S Gambhir,et al.  Creating self-illuminating quantum dot conjugates , 2006, Nature Protocols.

[54]  Feng Liu,et al.  Near infrared long-persistent phosphorescence in SrAl2O4:Eu2+,Dy3+,Er3+ phosphors based on persistent energy transfer , 2009 .

[55]  Kami Kim,et al.  Bright and stable near infra-red fluorescent protein for in vivo imaging , 2011, Nature Biotechnology.

[56]  Maureen A Walling,et al.  Quantum Dots for Live Cell and In Vivo Imaging , 2009, International journal of molecular sciences.

[57]  K. Byrappa,et al.  Handbook of Hydrothermal Technology: A Technology for Crystal Growth and Materials Processing , 2001 .

[58]  R. Haugland.  The Handbook: A Guide to Fluorescent Probes and Labeling Technologies , 2005 .

[59]  Qiang Zhao,et al.  Functional near infrared-emitting Cr3+/Pr3+ co-doped zinc gallogermanate persistent luminescent nanoparticles with superlong afterglow for in vivo targeted bioimaging. , 2013, Journal of the American Chemical Society.

[60]  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.

[61]  Jie Shen,et al.  Tunable near infrared to ultraviolet upconversion luminescence enhancement in (α-NaYF4 :Yb,Tm)/CaF2 core/shell nanoparticles for in situ real-time recorded biocompatible photoactivation. , 2013, Small.

[62]  M. Michaelis,et al.  Interaction of folate-conjugated human serum albumin (HSA) nanoparticles with tumour cells. , 2011, International journal of pharmaceutics.

[63]  Jeffrey L. Wrana,et al.  Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling , 2005, Nature Reviews Molecular Cell Biology.

[64]  D. Scherman,et al.  In vivo imaging with persistent luminescence silicate-based nanoparticles , 2013 .

[65]  P. Hwu,et al.  Visualizing fewer than 10 mouse T cells with an enhanced firefly luciferase in immunocompetent mouse models of cancer , 2008, Proceedings of the National Academy of Sciences.

[66]  K. Lukyanov,et al.  Diversity and evolution of the green fluorescent protein family , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[67]  Guosong Hong,et al.  Multifunctional in vivo vascular imaging using near-infrared II fluorescence , 2012, Nature Medicine.

[68]  J. Ding,et al.  Ultrafine ferrite particles prepared by coprecipitation/mechanical milling , 2000 .

[69]  T. Gjøen,et al.  A role for scavenger receptors in phagocytosis of protein-coated particles in rainbow trout head kidney macrophages. , 1998, Developmental and comparative immunology.

[70]  Erlong Zhang,et al.  A review of NIR dyes in cancer targeting and imaging. , 2011, Biomaterials.

[71]  Didier Gourier,et al.  Nanoprobes with near-infrared persistent luminescence for in vivo imaging , 2007, Proceedings of the National Academy of Sciences.

[72]  S. Jacques.  Optical properties of biological tissues: a review , 2013, Physics in medicine and biology.

[73]  B. Kukliński,et al.  Cr-related centers in Gd3Ga5O12 polycrystals , 2009 .

[74]  P. Mutin,et al.  Organic–inorganic hybrid materials based on organophosphorus coupling molecules: from metal phosphonates to surface modification of oxides , 2003 .

[75]  R. Weissleder,et al.  Imaging in the era of molecular oncology , 2008, Nature.

[76]  H. Kamiya,et al.  Analysis of the action mechanism of polymer dispersant on dense ethanol alumina suspension using colloidal probe AFM , 2005 .

[77]  V. Apostolopoulos,et al.  Delivery of DNA vaccines: an overview on the use of biodegradable polymeric and magnetic nanoparticles. , 2010, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

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

[79]  Mauro Ferrari,et al.  The association of silicon microparticles with endothelial cells in drug delivery to the vasculature. , 2009, Biomaterials.

[80]  W. D. de Vos,et al.  Multiparametric Flow Cytometry and Cell Sorting for the Assessment of Viable, Injured, and Dead Bifidobacterium Cells during Bile Salt Stress , 2002, Applied and Environmental Microbiology.

[81]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[82]  Jin Y. Xie,et al.  Human serum albumin coated iron oxide nanoparticles for efficient cell labeling. , 2010, Chemical communications.

[83]  S. Dimmeler,et al.  Cell-based therapies and imaging in cardiology , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[84]  P. Hoffer.  Status of gallium-67 in tumor detection. , 1980, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[86]  P. Choyke,et al.  PET/CT Imaging and Radioimmunotherapy of Prostate Cancer. , 2011, Seminars in nuclear medicine.

[87]  Valérie Cabuil,et al.  Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging. , 2005, Journal of the American Chemical Society.

[88]  Gary R. Whittaker,et al.  Influenza Virus Can Enter and Infect Cells in the Absence of Clathrin-Mediated Endocytosis , 2002, Journal of Virology.

[89]  Zhuang Liu,et al.  Upconversion nanoparticles and their composite nanostructures for biomedical imaging and cancer therapy. , 2013, Nanoscale.

[90]  B. Bhushan,et al.  Alkylphosphonate modified aluminum oxide surfaces. , 2006, The journal of physical chemistry. B.

[91]  John Condeelis,et al.  Macrophages: Obligate Partners for Tumor Cell Migration, Invasion, and Metastasis , 2006, Cell.

[92]  C. Serna,et al.  Surface characterisation of dextran-coated iron oxide nanoparticles prepared by laser pyrolysis and coprecipitation , 2005 .

[93]  Xiaoyuan Chen,et al.  Near-infrared quantum dots as optical probes for tumor imaging. , 2010, Current topics in medicinal chemistry.

[94]  R. Haugland,et al.  Alexa Dyes, a Series of New Fluorescent Dyes that Yield Exceptionally Bright, Photostable Conjugates , 1999, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[95]  Zhen Cheng,et al.  Ultrasmall near-infrared non-cadmium quantum dots for in vivo tumor imaging. , 2010, Small.

[96]  K. Holmberg,et al.  Dispersant adsorption and viscoelasticity of alumina suspensions measured by quartz crystal microbalance with dissipation monitoring and in situ dynamic rheology. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[97]  N. Buske,et al.  Biocompatible magnetic core/shell nanoparticles , 2002 .

[98]  Y. Toyozawa,et al.  Tunneling recombination of trapped electrons and holes in KCl:AgCl and KCl:TlCl , 1974 .

[99]  O. Lyckfeldt,et al.  Stabilization of alumina with polyelectrolyte and comb copolymer in solvent mixtures of water and alcohols , 2009 .

[100]  T. Deerinck,et al.  Quantum Dots for Tracking Dendritic Cells and Priming an Immune Response In Vitro and In Vivo , 2008, PloS one.

[101]  Petri Välisuo,et al.  A Review of Indocyanine Green Fluorescent Imaging in Surgery , 2012, Int. J. Biomed. Imaging.

[102]  J. Penfold,et al.  The application of the specular reflection of neutrons to the study of surfaces and interfaces , 1990 .

[103]  W. Soboyejo,et al.  A TEM study of functionalized magnetic nanoparticles targeting breast cancer cells , 2006 .

[104]  Kirsten Sandvig,et al.  Endocytosis and intracellular transport of nanoparticles: Present knowledge and need for future studies , 2011 .

[105]  J. Rao,et al.  Self-luminescing BRET-FRET near infrared dots for in vivo lymph node mapping and tumor imaging , 2012, Nature Communications.

[106]  Suresh C. Sharma,et al.  Effect of Concentration of Ammonium Poly(acrylate) Dispersant and MgO on Coagulation Characteristics of Aqueous Alumina Direct Coagulation Casting Slurries , 2008 .

[107]  Monya Baker,et al.  Whole-animal imaging: The whole picture , 2010, Nature.

[108]  J. Ueda,et al.  Enhancement of Red Persistent Luminescence in Cr3+-Doped ZnGa2O4 Phosphors by Bi2O3 Codoping , 2013 .

[109]  Roger A. Pedersen,et al.  Early Cell Fate Decisions of Human Embryonic Stem Cells and Mouse Epiblast Stem Cells Are Controlled by the Same Signalling Pathways , 2009, PloS one.

[110]  Bernard Valeur,et al.  A Brief History of Fluorescence and Phosphorescence before the Emergence of Quantum Theory , 2011 .

[111]  G. Battaglia,et al.  Endocytosis at the nanoscale. , 2012, Chemical Society reviews.

[112]  W. Chan,et al.  Bioimaging: illuminating the deep. , 2013, Nature materials.

[113]  Sanjiv S Gambhir,et al.  Self-illuminating quantum dot conjugates for in vivo imaging , 2006, Nature Biotechnology.

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

[115]  A. Aderem,et al.  Mechanisms of phagocytosis in macrophages. , 1999, Annual review of immunology.

[116]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[117]  V. Verkhusha,et al.  Near-infrared fluorescent proteins for multicolor in vivo imaging , 2013, Nature Methods.

[118]  J. Lewis,et al.  Comb Polymer Architecture, Ionic Strength, and Particle Size Effects on the BaTiO3 Suspension Stability , 2009 .

[119]  Ari Helenius,et al.  Virus entry by macropinocytosis , 2009, Nature Cell Biology.

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

[121]  Z. Pan,et al.  Long-lasting near-infrared persistent luminescence from β-Ga2O3:Cr3+ nanowire assemblies , 2011 .

[122]  Jun Fang,et al.  The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. , 2011, Advanced drug delivery reviews.

[123]  Jinwoo Cheon,et al.  Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. , 2005, Journal of the American Chemical Society.

[124]  Chunhua Yan,et al.  Colloidal synthesis and blue based multicolor upconversion emissions of size and composition controlled monodisperse hexagonal NaYF4:Yb,Tm nanocrystals. , 2010, Nanoscale.

[125]  K. Leong,et al.  Near-Infrared Fluorescent Nanoprobes for in Vivo Optical Imaging , 2012, Nanomaterials.

[126]  J. Yarger,et al.  NMR Characterization of Phosphonic Acid Capped SnO2 Nanoparticles , 2007 .

[127]  A. Clearfield,et al.  A family of microporous materials formed by Sn(IV) phosphonate nanoparticles. , 2005, Journal of the American Chemical Society.

[128]  A. Hoffmann,et al.  Phosphonic acid monolayers for binding of bioactive molecules to titanium surfaces. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[129]  Yasuyoshi Watanabe,et al.  [Molecular imaging for drug development]. , 2007, Brain and nerve = Shinkei kenkyu no shinpo.

[130]  Jianan Y. Qu,et al.  Fluorescence spectroscopy of biological tissue: single- and two-photon excitation , 2004, SPIE BiOS.

[131]  Beibei Zhang,et al.  Surface functionalization of zinc oxide by carboxyalkylphosphonic acid self-assembled monolayers. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[132]  Kevin Welsher,et al.  Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window , 2011, Proceedings of the National Academy of Sciences.

[133]  C. Contag,et al.  Emission spectra of bioluminescent reporters and interaction with mammalian tissue determine the sensitivity of detection in vivo. , 2005, Journal of biomedical optics.

[134]  R K Jain,et al.  Transport of molecules, particles, and cells in solid tumors. , 1999, Annual review of biomedical engineering.

[135]  S. Gambhir,et al.  Molecular imaging in living subjects: seeing fundamental biological processes in a new light. , 2003, Genes & development.

[136]  M. Zimmer.  GFP: from jellyfish to the Nobel prize and beyond. , 2009, Chemical Society reviews.

[137]  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.

[138]  A. Meijerink,et al.  Photostimulated luminescence and thermally stimulated luminescence of some new X-ray storage phosphors , 1991 .

[139]  Richard L Ehman,et al.  Blueprint for imaging in biomedical research. , 2007, Radiology.

[140]  B. C. Grabmaier,et al.  The afterglow mechanism of chromium-doped gadolinium gallium garnet , 1993 .

[141]  Chunhai Fan,et al.  The cytotoxicity of cadmium-based quantum dots. , 2012, Biomaterials.

[142]  William M. Yen,et al.  Inorganic Phosphors: Compositions, Preparation and Optical Properties , 2004 .

[143]  S. Subramaniam,et al.  Chemoattractant Signaling between Tumor Cells and Macrophages Regulates Cancer Cell Migration, Metastasis and Neovascularization , 2009, PloS one.

[144]  D. Ho,et al.  Characterization of Metal-Oxide Nanoparticles: Synthesis and Dispersion in Polymeric Coatings. , 2002 .

[145]  Hiroshi Maeda,et al.  Tumor-selective delivery of macromolecular drugs via the EPR effect: background and future prospects. , 2010, Bioconjugate chemistry.

[146]  Zhuang Liu,et al.  A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice. , 2009, Nature nanotechnology.

[147]  V. Muzykantov,et al.  Multifunctional Nanoparticles: Cost Versus Benefit of Adding Targeting and Imaging Capabilities , 2012, Science.