Gd3+ complex-modified NaLuF4-based upconversion nanophosphors for trimodality imaging of NIR-to-NIR upconversion luminescence, X-Ray computed tomography and magnetic resonance.

Multimodality molecular imaging has recently attracted much attention, because it can take advantage of individual imaging modalities by fusing together information from several molecular imaging techniques. Herein, we report a multifunctional lanthanide-based nanoparticle for near-infrared to near-infrared (NIR-to-NIR) upconversion luminescence (UCL), X-ray computed tomography (CT) and T(1)-enhanced magnetic resonance (MR) trimodality in-vivo imaging. By careful selection of the lanthanide elements, core-shell structured lanthanide-based nanoparticles, NaLuF(4):Yb(3+),Tm(3+)@SiO(2)-GdDTPA nanoparticles (UCNP@SiO(2)-GdDTPA) have been designed and synthesized. We also prove that the application of UCNP@SiO(2)-GdDTPA for NIR-to-NIR UCL, CT and MRI multi-modality in-vivo imaging can be established successfully. In addition, the biological toxicity of UCNP@SiO(2)-GdDTPA is evaluated by the methyl thiazolyl tetrazolium (MTT) assay and histological analysis of viscera sections.

[1]  J. Yee,et al.  Accuracy of ct colonography for detection of large adenomas and cancers , 2009 .

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

[3]  Lianzhou Wang,et al.  Positive and Negative Lattice Shielding Effects Co‐existing in Gd (III) Ion Doped Bifunctional Upconversion Nanoprobes , 2011 .

[4]  H. Engler,et al.  PET imaging of amyloid deposition in patients with mild cognitive impairment , 2008, Neurobiology of Aging.

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

[6]  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.

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

[8]  Jun Lin,et al.  Rare earth fluoride nano-/microcrystals: synthesis, surface modification and application , 2010 .

[9]  Younan Xia,et al.  Modifying the Surface Properties of Superparamagnetic Iron Oxide Nanoparticles through A Sol−Gel Approach , 2002 .

[10]  M. Botta,et al.  High relaxivity gadolinium hydroxypyridonate-viral capsid conjugates: nanosized MRI contrast agents. , 2008, Journal of the American Chemical Society.

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

[12]  Eung Yeop Kim,et al.  Self-confirming "AND" logic nanoparticles for fault-free MRI. , 2010, Journal of the American Chemical Society.

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

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

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

[16]  Lehui Lu,et al.  A high-performance ytterbium-based nanoparticulate contrast agent for in vivo X-ray computed tomography imaging. , 2012, Angewandte Chemie.

[17]  Angelique Louie,et al.  Multimodality imaging probes: design and challenges. , 2010, Chemical reviews.

[18]  Chenjie Xu,et al.  PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles , 2008, Journal of Nuclear Medicine.

[19]  Dar-Bin Shieh,et al.  In vitro and in vivo studies of FePt nanoparticles for dual modal CT/MRI molecular imaging. , 2010, Journal of the American Chemical Society.

[20]  Markus P. Hehlen,et al.  Power dependence of upconversion luminescence in lanthanide and transition-metal-ion systems , 2000 .

[21]  Greg J. Stanisz,et al.  Size-Tunable, Ultrasmall NaGdF4 Nanoparticles: Insights into Their T1 MRI Contrast Enhancement , 2011 .

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

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

[24]  Borys Shuter,et al.  Hybrid lanthanide nanoparticles with paramagnetic shell coated on upconversion fluorescent nanocrystals. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[25]  Byeong-Hyeok Sohn,et al.  Specific targeting, cell sorting, and bioimaging with smart magnetic silica core-shell nanomaterials. , 2006, Small.

[26]  Yun Sun,et al.  Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles. , 2011, Biomaterials.

[27]  Zhengquan Li,et al.  An efficient and user-friendly method for the synthesis of hexagonal-phase NaYF4:Yb, Er/Tm nanocrystals with controllable shape and upconversion fluorescence , 2008, Nanotechnology.

[28]  Dong Liang,et al.  A chelator-free multifunctional [64Cu]CuS nanoparticle platform for simultaneous micro-PET/CT imaging and photothermal ablation therapy. , 2010, Journal of the American Chemical Society.

[29]  Helmut Schäfer,et al.  Upconverting nanoparticles. , 2011, Angewandte Chemie.

[30]  Jun Lin,et al.  Synthesis of Magnetic, Up‐Conversion Luminescent, and Mesoporous Core–Shell‐Structured Nanocomposites as Drug Carriers , 2010 .

[31]  Jie Zheng,et al.  Luminescent gold nanoparticles with efficient renal clearance. , 2011, Angewandte Chemie.

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

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

[34]  Seulki Lee,et al.  Peptides and peptide hormones for molecular imaging and disease diagnosis. , 2010, Chemical reviews.

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

[36]  D. Townsend.  Multimodality imaging of structure and function , 2008, Physics in medicine and biology.

[37]  N. Logothetis.  What we can do and what we cannot do with fMRI , 2008, Nature.

[38]  Klaas Nicolay,et al.  Nanoparticulate assemblies of amphiphiles and diagnostically active materials for multimodality imaging. , 2009, Accounts of chemical research.

[39]  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.

[40]  Mingdong Huang,et al.  Amine-functionalized lanthanide-doped KGdF4 nanocrystals as potential optical/magnetic multimodal bioprobes. , 2012, Journal of the American Chemical Society.

[41]  Zhenyuan Zhang,et al.  Size-dependent melting of silica-encapsulated gold nanoparticles. , 2002, Journal of the American Chemical Society.

[42]  Yadong Li,et al.  Upconversion luminescence of monodisperse CaF2:Yb(3+)/Er(3+) nanocrystals. , 2009, Journal of the American Chemical Society.

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

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

[45]  S. Cherry,et al.  Simultaneous in vivo positron emission tomography and magnetic resonance imaging , 2008, Proceedings of the National Academy of Sciences.

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

[47]  Taeghwan Hyeon,et al.  Long-term real-time tracking of lanthanide ion doped upconverting nanoparticles in living cells. , 2011, Angewandte Chemie.

[48]  Hao Hong,et al.  cRGD-functionalized, DOX-conjugated, and ⁶⁴Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging. , 2011, Biomaterials.