Water-stable NaLuF4-based upconversion nanophosphors with long-term validity for multimodal lymphatic imaging.

Multimodal imaging is rapidly becoming an important tool for biomedical applications because it can compensate for the deficiencies of individual imaging modalities. Herein, multifunctional NaLuF(4)-based upconversion nanoparticles (Lu-UCNPs) were synthesized though a facile one-step microemulsion method under ambient condition. The doping of lanthanide ions (Gd(3+), Yb(3+) and Er(3+)/Tm(3+)) endows the Lu-UCNPs with high T(1)-enhancement, bright upconversion luminescence (UCL) emissions, and excellent X-ray absorption coefficient. Moreover, the as-prepared Lu-UCNPs are stable in water for more than six months, due to the protection of sodium glutamate and diethylene triamine pentacetate acid (DTPA) coordinating ligands on the surface. Lu-UCNPs have been successfully applied to the trimodal CT/MR/UCL lymphatic imaging on the modal of small animals. It is worth noting that Lu-UCNPs could be used for imaging even after preserving for over six months. In vitro transmission electron microscope (TEM), methyl thiazolyl tetrazolium (MTT) assay and histological analysis demonstrated that Lu-UCNPs exhibited low toxicity on living systems. Therefore, Lu-UCNPs could be multimodal agents for CT/MR/UCL imaging, and the concept can be served as a platform technology for the next-generation of probes for multimodal imaging.

[1]  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.

[2]  O. Bunk,et al.  Ptychographic X-ray computed tomography at the nanoscale , 2010, Nature.

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

[4]  Dongmei Wu,et al.  Core-shell NaYF4:Yb3+,Tm3+@FexOy nanocrystals for dual-modality T2-enhanced magnetic resonance and NIR-to-NIR upconversion luminescent imaging of small-animal lymphatic node. , 2011, Biomaterials.

[5]  Yun Sun,et al.  Fluorine-18-labeled Gd3+/Yb3+/Er3+ co-doped NaYF4 nanophosphors for multimodality PET/MR/UCL imaging. , 2011, Biomaterials.

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

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

[8]  Xiaogang Liu,et al.  Recent Advances in the Chemistry of Lanthanide‐Doped Upconversion Nanocrystals , 2009 .

[9]  Yanqing Hua,et al.  Multifunctional nanoprobes for upconversion fluorescence, MR and CT trimodal imaging. , 2012, Biomaterials.

[10]  Liangping Zhou,et al.  Controlled synthesis of uniform and monodisperse upconversion core/mesoporous silica shell nanocomposites for bimodal imaging. , 2012, Chemistry.

[11]  Chao Wang,et al.  Single-band upconversion emission in lanthanide-doped KMnF3 nanocrystals. , 2011, Angewandte Chemie.

[12]  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.

[13]  Qing Peng,et al.  Lanthanide-doped nanocrystals: synthesis, optical-magnetic properties, and applications. , 2011, Accounts of chemical research.

[14]  Shuk Han Cheng,et al.  Polymer-coated NaYF₄:Yb³⁺, Er³⁺ upconversion nanoparticles for charge-dependent cellular imaging. , 2011, ACS nano.

[15]  B. Misselwitz.  MR contrast agents in lymph node imaging. , 2006, European journal of radiology.

[16]  Karthikeyan Subramani,et al.  Magnetic resonance imaging tracking of stem cells in vivo using iron oxide nanoparticles as a tool for the advancement of clinical regenerative medicine. , 2011, Chemical reviews.

[17]  Zhuang Liu,et al.  Near-infrared light induced in vivo photodynamic therapy of cancer based on upconversion nanoparticles. , 2011, Biomaterials.

[18]  Nayoun Won,et al.  Multiplexed near-infrared in vivo imaging complementarily using quantum dots and upconverting NaYF4:Yb3+,Tm3+ nanoparticles. , 2011, Chemical communications.

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

[20]  Kai Yang,et al.  Facile preparation of multifunctional upconversion nanoprobes for multimodal imaging and dual-targeted photothermal therapy. , 2011, Angewandte Chemie.

[21]  Wei Feng,et al.  Cubic sub-20 nm NaLuF(4)-based upconversion nanophosphors for high-contrast bioimaging in different animal species. , 2012, Biomaterials.

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

[23]  Kai Yang,et al.  Highly-sensitive multiplexed in vivo imaging using pegylated upconversion nanoparticles , 2010 .

[24]  Yun Sun,et al.  Fluorine-18 labeled rare-earth nanoparticles for positron emission tomography (PET) imaging of sentinel lymph node. , 2011, Biomaterials.

[25]  Louis A. Cuccia,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.

[26]  Renren Deng,et al.  Tuning upconversion through energy migration in core-shell nanoparticles. , 2011, Nature materials.

[27]  Qian Liu,et al.  18F-Labeled magnetic-upconversion nanophosphors via rare-Earth cation-assisted ligand assembly. , 2011, ACS nano.

[28]  Jianhua Hao,et al.  Water dispersible ultra-small multifunctional KGdF4:Tm3+, Yb3+ nanoparticles with near-infrared to near-infrared upconversion , 2011 .

[29]  Qian Liu,et al.  Multifunctional rare-earth self-assembled nanosystem for tri-modal upconversion luminescence /fluorescence /positron emission tomography imaging. , 2011, Biomaterials.

[30]  P. Choyke,et al.  In vivo multiple color lymphatic imaging using upconverting nanocrystals , 2009 .

[31]  Xiaohong Sun,et al.  Fabrication of Ag@SiO(2)@Y(2)O(3):Er nanostructures for bioimaging: tuning of the upconversion fluorescence with silver nanoparticles. , 2010, Journal of the American Chemical Society.

[32]  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.

[33]  Dan Wang,et al.  Using 915 nm laser excited Tm³+/Er³+/Ho³+- doped NaYbF4 upconversion nanoparticles for in vitro and deeper in vivo bioimaging without overheating irradiation. , 2011, ACS nano.

[34]  Shan Jiang,et al.  Multicolor Core/Shell‐Structured Upconversion Fluorescent Nanoparticles , 2008 .

[35]  Ick Chan Kwon,et al.  Multifunctional nanoparticles for multimodal imaging and theragnosis. , 2012, Chemical Society reviews.

[36]  Geoffrey A Ozin,et al.  Synthesis of ligand-free colloidally stable water dispersible brightly luminescent lanthanide-doped upconverting nanoparticles. , 2011, Nano letters.

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

[38]  Peter Caravan,et al.  Protein-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agents: design and mechanism of action. , 2009, Accounts of chemical research.

[39]  Xiaohan Liu,et al.  A "neck-formation" strategy for an antiquenching magnetic/upconversion fluorescent bimodal cancer probe. , 2010, Chemistry.

[40]  Jun Lin,et al.  Up-conversion cell imaging and pH-induced thermally controlled drug release from NaYF4/Yb3+/Er3+@hydrogel core-shell hybrid microspheres. , 2012, ACS nano.

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

[42]  F. V. Veggel,et al.  Hard Proof of the NaYF4/NaGdF4 Nanocrystal Core/ Shell Structure [J. Am. Chem. Soc. 2009, 131, 14644―14645] , 2010 .

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

[44]  Tristan Barrett,et al.  Multimodal nanoprobes for radionuclide and five-color near-infrared optical lymphatic imaging. , 2007, ACS nano.

[45]  Wei Feng,et al.  Core-shell Fe3O4@NaLuF4:Yb,Er/Tm nanostructure for MRI, CT and upconversion luminescence tri-modality imaging. , 2012, Biomaterials.

[46]  Gregory S Harms,et al.  Upconverting nanoparticles for nanoscale thermometry. , 2011, Angewandte Chemie.

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

[48]  Daxiang Cui,et al.  Dual Phase‐Controlled Synthesis of Uniform Lanthanide‐Doped NaGdF4 Upconversion Nanocrystals Via an OA/Ionic Liquid Two‐Phase System for In Vivo Dual‐Modality Imaging , 2011 .

[49]  Chunhua Yan,et al.  Luminescent rare earth nanomaterials for bioprobe applications. , 2008, Dalton transactions.

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

[51]  Jan Grimm,et al.  An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles , 2006, Nature materials.

[52]  Jun Lin,et al.  Monodisperse core-shell structured up-conversion Yb(OH)CO₃@YbPO₄:Er³+ hollow spheres as drug carriers. , 2011, Biomaterials.