Nanoparticles for multi-modality cancer diagnosis: Simple protocol for self-assembly of gold nanoclusters mediated by gadolinium ions.

It is essential to develop a simple synthetic strategy to improve the quality of multifunctional contrast agents for cancer diagnosis. Herein, we report a time-saving method for gadolinium (Gd3+) ions-mediated self-assembly of gold nanoclusters (GNCs) into monodisperse spherical nanoparticles (GNCNs) under mild conditions. The monodisperse, regular and colloidal stable GNCNs were formed via selectively inducing electrostatic interactions between negatively-charged carboxylic groups of gold nanoclusters and trivalent cations of gadolinium in aqueous solution. In this way, the Gd3+ ions were chelated into GNCNs without the use of molecular gadolinium chelates. With the co-existence of GNCs and Gd3+ ions, the formed GNCNs exhibit significant luminescence intensity enhancement for near-infrared fluorescence (NIRF) imaging, high X-ray attenuation for computed tomography (CT) imaging and reasonable r1 relaxivity for magnetic resonance (MR) imaging. The excellent biocompatibility of the GNCNs was proved both in vitro and in vivo. Meanwhile, the GNCNs also possess unique NIRF/CT/MR imaging ability in A549 tumor-bearing mice. In a nutshell, the simple and safe GNCNs hold great potential for tumor multi-modality clinical diagnosis.

[1]  Chen Zhou,et al.  Luminescent gold nanoparticles with pH-dependent membrane adsorption. , 2011, Journal of the American Chemical Society.

[2]  Cui Tang,et al.  Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. , 2010, Biomaterials.

[3]  Daxiang Cui,et al.  Glutathione-capped fluorescent gold nanoclusters for dual-modal fluorescence/X-ray computed tomography imaging. , 2013, Journal of materials chemistry. B.

[4]  Wei Feng,et al.  Lanthanide-based nanocrystals as dual-modal probes for SPECT and X-ray CT imaging. , 2014, Biomaterials.

[5]  P. Kamat,et al.  Metal-cluster-sensitized solar cells. A new class of thiolated gold sensitizers delivering efficiency greater than 2%. , 2013, Journal of the American Chemical Society.

[6]  Christophe Demattei,et al.  Impact of the Adaptive Statistical Iterative Reconstruction Technique on Radiation Dose and Image Quality in Bone SPECT/CT , 2016, The Journal of Nuclear Medicine.

[7]  Jianping Xie,et al.  Protein-directed synthesis of highly fluorescent gold nanoclusters. , 2009, Journal of the American Chemical Society.

[8]  Lingzhou Zhao,et al.  99mTc-labelled multifunctional polyethylenimine-entrapped gold nanoparticles for dual mode SPECT and CT imaging , 2018, Artificial cells, nanomedicine, and biotechnology.

[9]  H. Frey,et al.  Water‐Soluble Fluorescent Ag Nanoclusters Obtained from Multiarm Star Poly(acrylic acid) as “Molecular Hydrogel” Templates , 2007 .

[10]  Duyang Gao,et al.  Hybrid gold-gadolinium nanoclusters for tumor-targeted NIRF/CT/MRI triple-modal imaging in vivo. , 2013, Nanoscale.

[11]  Eleonore Fröhlich,et al.  The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles , 2012, International journal of nanomedicine.

[12]  Li Shang,et al.  Intracellular thermometry by using fluorescent gold nanoclusters. , 2013, Angewandte Chemie.

[13]  Mingwu Shen,et al.  Multifunctional PEGylated Multiwalled Carbon Nanotubes for Enhanced Blood Pool and Tumor MR Imaging , 2014, Advanced healthcare materials.

[14]  Yingge Zhang,et al.  Insights into the Distinguishing Stress-induced Cytotoxicity of Chiral Gold Nanoclusters and the Relationship with GSTP1 , 2015, Theranostics.

[15]  Tarasankar Pal,et al.  Interparticle coupling effect on the surface plasmon resonance of gold nanoparticles: from theory to applications. , 2007, Chemical reviews.

[16]  J. Taleb,et al.  Assembly of Double-Hydrophilic Block Copolymers Triggered by Gadolinium Ions: New Colloidal MRI Contrast Agents. , 2016, Nano letters.

[17]  Jianping Xie,et al.  Enhanced tumor accumulation of sub-2 nm gold nanoclusters for cancer radiation therapy. , 2014, Advanced healthcare materials.

[18]  F. Mérola,et al.  Self-Assembled Gold Nanoclusters for Bright Fluorescence Imaging and Enhanced Drug Delivery. , 2016, ACS nano.

[19]  R. Jin,et al.  Thiolate-protected Au(20) clusters with a large energy gap of 2.1 eV. , 2009, Journal of the American Chemical Society.

[20]  N. Pirie,et al.  THE TITRATION CURVE OF GLUTATHIONE , 1929 .

[21]  Jinchao Zhang,et al.  In vivo tumor-targeted dual-modal fluorescence/CT imaging using a nanoprobe co-loaded with an aggregation-induced emission dye and gold nanoparticles. , 2015, Biomaterials.

[22]  Zhuang Liu,et al.  Engineering of Multifunctional Nano‐Micelles for Combined Photothermal and Photodynamic Therapy Under the Guidance of Multimodal Imaging , 2014 .

[23]  M. Blanca,et al.  Intracellular accumulation and immunological properties of fluorescent gold nanoclusters in human dendritic cells. , 2015, Biomaterials.

[24]  Yukio Hinatsu,et al.  Reversible mechanochromic luminescence of [(C6F5Au)2(mu-1,4-diisocyanobenzene)]. , 2008, Journal of the American Chemical Society.

[25]  H. Tan,et al.  Plasmonic gold nanocrosses with multidirectional excitation and strong photothermal effect. , 2011, Journal of the American Chemical Society.

[26]  Yunpeng Huang,et al.  Multifunctional dendrimer-entrapped gold nanoparticles for dual mode CT/MR imaging applications. , 2013, Biomaterials.

[27]  Yong Hu,et al.  Hyaluronic acid-modified Fe3O4@Au core/shell nanostars for multimodal imaging and photothermal therapy of tumors. , 2015, Biomaterials.

[28]  H. Mattoussi,et al.  Growth of highly fluorescent polyethylene glycol- and zwitterion-functionalized gold nanoclusters. , 2013, ACS nano.

[29]  Jianping Xie,et al.  From aggregation-induced emission of Au(I)-thiolate complexes to ultrabright Au(0)@Au(I)-thiolate core-shell nanoclusters. , 2012, Journal of the American Chemical Society.

[30]  Xingyu Jiang,et al.  Gold nanoparticles for the colorimetric and fluorescent detection of ions and small organic molecules. , 2011, Nanoscale.

[31]  G. Pöpperl,et al.  Current Molecular Imaging of Spinal Tumors in Clinical Practice , 2011, Molecular medicine.

[32]  Jin Chang,et al.  Intrinsically Radioactive [64Cu]CuInS/ZnS Quantum Dots for PET and Optical Imaging: Improved Radiochemical Stability and Controllable Cerenkov Luminescence , 2014, ACS nano.

[33]  Gold Nanoparticles Coated with Gd-Chelate as a Potential CT/MRI Bimodal Contrast Agent , 2010 .

[34]  J. Lee,et al.  Assembly of Nanoions via Electrostatic Interactions: Ion-Like Behavior of Charged Noble Metal Nanoclusters , 2014, Scientific Reports.

[35]  R. Jin,et al.  Thiolate‐Protected Aun Nanoclusters as Catalysts for Selective Oxidation and Hydrogenation Processes , 2010, Advanced materials.

[36]  Zhuang Liu,et al.  Photosensitizer-Conjugated Albumin-Polypyrrole Nanoparticles for Imaging-Guided In Vivo Photodynamic/Photothermal Therapy. , 2015, Small.

[37]  Andrew Tsourkas,et al.  Gadolinium-conjugated dendrimer nanoclusters as a tumor-targeted T1 magnetic resonance imaging contrast agent. , 2010, Angewandte Chemie.

[38]  T. Andresen,et al.  In vivo evaluation of PEGylated 64Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[39]  Francis Vocanson,et al.  Gadolinium chelate coated gold nanoparticles as contrast agents for both X-ray computed tomography and magnetic resonance imaging. , 2008, Journal of the American Chemical Society.

[40]  H. Schmidbaur,et al.  Ludwig Mond Lecture. High-carat gold compounds , 1995 .

[41]  Chao Li,et al.  Gold Nanoclusters‐Based Nanoprobes for Simultaneous Fluorescence Imaging and Targeted Photodynamic Therapy with Superior Penetration and Retention Behavior in Tumors , 2015 .

[42]  R. Jin,et al.  Stability of the Two Au-S Binding Modes in Au(25)(SG)(18) Nanoclusters Probed by NMR and Optical Spectroscopy. , 2009, ACS nano.

[43]  Mingwu Shen,et al.  Targeted tumor CT imaging using folic acid-modified PEGylated dendrimer-entrapped gold nanoparticles , 2013 .

[44]  H. Ramanarayan,et al.  An experimental and theoretical investigation of the anisotropic branching in gold nanocrosses. , 2016, Nanoscale.

[45]  Zoraida P. Aguilar,et al.  Assessment and comparison of magnetic nanoparticles as MRI contrast agents in a rodent model of human hepatocellular carcinoma. , 2012, Contrast media & molecular imaging.

[46]  Shuming Nie,et al.  Next-generation quantum dots , 2009, Nature Biotechnology.

[47]  Jie Zheng,et al.  Near-infrared emitting radioactive gold nanoparticles with molecular pharmacokinetics. , 2012, Angewandte Chemie.

[48]  Chia-Wei Wang,et al.  Fluorescent gold nanoclusters: recent advances in sensing and imaging. , 2015, Analytical chemistry.

[49]  D. Cui,et al.  MMP2-Targeting and Redox-Responsive PEGylated Chlorin e6 Nanoparticles for Cancer Near-Infrared Imaging and Photodynamic Therapy. , 2016, ACS applied materials & interfaces.

[50]  Jinwoo Cheon,et al.  Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging , 2007, Nature Medicine.

[51]  X. Guével.  Recent Advances on the Synthesis of Metal Quantum Nanoclusters and Their Application for Bioimaging , 2014 .

[52]  Yuliang Zhao,et al.  TPGS-stabilized NaYbF4:Er upconversion nanoparticles for dual-modal fluorescent/CT imaging and anticancer drug delivery to overcome multi-drug resistance. , 2015, Biomaterials.

[53]  V. Torchilin,et al.  Diacyllipid-Polymer Micelles as Nanocarriers for Poorly Soluble Anticancer Drugs , 2002 .

[54]  Helmuth Möhwald,et al.  ZnO-Based Nanoplatforms for Labeling and Treatment of Mouse Tumors without Detectable Toxic Side Effects. , 2016, ACS nano.

[55]  Yuan Cheng,et al.  Destabilization of Thiolated Gold Clusters for the Growth of Single‐Crystalline Gold Nanoparticles and Their Self‐Assembly for SERS Detection , 2015 .

[56]  Jing Zhou,et al.  Gadolinium complex and phosphorescent probe-modified NaDyF4 nanorods for T1- and T2-weighted MRI/CT/phosphorescence multimodality imaging. , 2014, Biomaterials.

[57]  Mingwu Shen,et al.  Targeted CT/MR dual mode imaging of tumors using multifunctional dendrimer-entrapped gold nanoparticles. , 2013, Biomaterials.

[58]  Chen Zhou,et al.  Different sized luminescent gold nanoparticles. , 2012, Nanoscale.

[59]  Ben Zhong Tang,et al.  Aggregation-induced emission. , 2011, Chemical Society reviews.

[60]  Huiru Ma,et al.  Facile preparation of magnetic γ-Fe₂O₃/TiO₂ Janus hollow bowls with efficient visible-light photocatalytic activities by asymmetric shrinkage. , 2012, Nanoscale.