Gd-Dots with Strong Ligand-Water Interaction for Ultrasensitive Magnetic Resonance Renography.

Magnetic resonance imaging contrast agents with both significantly enhanced relaxivity and minimal safety risk are of great importance for sensitive clinical diagnosis, but have rarely been reported. Herein, we present a simple strategy to improve relaxivity by introducing surface ligands with strong interaction to water molecules. As a proof of concept, NaGdF4 nanoparticles (NPs) capped by poly(acrylic acid) (PAA) show superior relaxivity to those capped by polyethylenimine and polyethylene glycol, which is attributed to the strong hydrogen-bond capacity of PAA to water molecules as revealed by theoretical calculation. Furthermore, benefiting from PAA and ultrasmall particle size, Gd-dots, namely PAA-capped GdOF NPs (2.1 ± 0.2 nm), are developed as a high-performance contrast agent, with a remarkable ionic relaxivity of ∼75 mM-1 s-1 in albumin solution at 0.5 T. These Gd-dots also exhibit efficient renal clearance with <3% of injected amount left 12 h post-injection. Ultrasensitive MR renography achieved with Gd-dots strongly suggests their great potential for practical applications.

[1]  Zijian Zhou,et al.  Geometrically confined ultrasmall gadolinium oxide nanoparticles boost the T(1) contrast ability. , 2016, Nanoscale.

[2]  Mauro Ferrari,et al.  Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast , 2010, Nature nanotechnology.

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

[4]  S. Dong,et al.  Alendronate as a robust anchor for ceria nanoparticle surface coating: facile binding and improved biological properties , 2014 .

[5]  R. Wu,et al.  Integrating Anatomic and Functional Dual-Mode Magnetic Resonance Imaging: Design and Applicability of a Bifunctional Contrast Agent. , 2016, ACS nano.

[6]  Jie Zheng,et al.  Clearance Pathways and Tumor Targeting of Imaging Nanoparticles. , 2015, ACS nano.

[7]  A. Almutairi,et al.  Compact Micellization: A Strategy for Ultrahigh T1 Magnetic Resonance Contrast with Gadolinium-Based Nanocrystals. , 2016, ACS nano.

[8]  Jianlin Shi,et al.  PEGylated NaHoF4 nanoparticles as contrast agents for both X-ray computed tomography and ultra-high field magnetic resonance imaging. , 2016, Biomaterials.

[9]  Liangping Zhou,et al.  Ultrasmall NaGdF4 Nanodots for Efficient MR Angiography and Atherosclerotic Plaque Imaging , 2014, Advanced materials.

[10]  Yongmin Chang,et al.  Paramagnetic ultrasmall gadolinium oxide nanoparticles as advanced T1 MRI contrast agent: account for large longitudinal relaxivity, optimal particle diameter, and in vivo T1 MR images. , 2009, ACS nano.

[11]  Robert E. Lenkinski,et al.  Gadolinium-Loaded Nanoparticles: New Contrast Agents for Magnetic Resonance Imaging , 2000 .

[12]  Enzo Terreno,et al.  Lanthanide(III) chelates for NMR biomedical applications , 1998 .

[13]  Peter Caravan,et al.  Strategies for increasing the sensitivity of gadolinium based MRI contrast agents. , 2006, Chemical Society reviews.

[14]  Diego R. Martín,et al.  Individual kidney blood flow measured with contrast-enhanced first-pass perfusion MR imaging. , 2008, Radiology.

[15]  V. Lee,et al.  Renal functional MRI: Are we ready for clinical application? , 2009, AJR. American journal of roentgenology.

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

[17]  Chao Zhang,et al.  Lanthanide Nanoparticles: From Design toward Bioimaging and Therapy. , 2015, Chemical reviews.

[18]  Nathan Blow,et al.  Functional Neuroscience: How to get ahead in imaging , 2009, Nature.

[19]  Teri W. Odom,et al.  High relaxivity Gd(III)-DNA gold nanostars: investigation of shape effects on proton relaxation. , 2015, ACS nano.

[20]  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.

[21]  K. Uvdal,et al.  High proton relaxivity for gadolinium oxide nanoparticles , 2006, Magnetic Resonance Materials in Physics, Biology and Medicine.

[22]  T. Pellegrino,et al.  Manganese doped-iron oxide nanoparticle clusters and their potential as agents for magnetic resonance imaging and hyperthermia. , 2016, Physical chemistry chemical physics : PCCP.

[23]  Zhangyou Yang,et al.  Photosensitizer-Loaded Branched Polyethylenimine-PEGylated Ceria Nanoparticles for Imaging-Guided Synchronous Photochemotherapy. , 2015, ACS applied materials & interfaces.

[24]  Joop A. Peters,et al.  MRI contrast agents based on dysprosium or holmium. , 2011, Progress in nuclear magnetic resonance spectroscopy.

[25]  Nicholas J Long,et al.  Lanthanides in magnetic resonance imaging. , 2006, Chemical Society reviews.

[26]  P. Choyke,et al.  Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. , 2008, Nanomedicine.

[27]  R. Lauffer,et al.  Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design , 1987 .

[28]  Peter Mansfield,et al.  Snapshot magnetic resonance imaging (Nobel lecture). , 2004, Angewandte Chemie.

[29]  Chunhua Yan,et al.  TbF3 nanoparticles as dual-mode contrast agents for ultrahigh field magnetic resonance imaging and X-ray computed tomography , 2016, Nano Research.

[30]  Raffaella Buonsanti,et al.  Exceptionally mild reactive stripping of native ligands from nanocrystal surfaces by using Meerwein's salt. , 2012, Angewandte Chemie.

[31]  L. Helm Relaxivity in paramagnetic systems: Theory and mechanisms , 2006 .

[32]  N. Rofsky,et al.  Basic MR relaxation mechanisms and contrast agent design , 2015, Journal of magnetic resonance imaging : JMRI.

[33]  Lanthanide Loaded Zeolites, Clays, and Mesoporous Silica Materials as MRI Probes , 2012 .

[34]  J. M. Kikkawa,et al.  A generalized ligand-exchange strategy enabling sequential surface functionalization of colloidal nanocrystals. , 2011, Journal of the American Chemical Society.

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

[36]  R. Lauffer,et al.  Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. , 1999, Chemical reviews.

[37]  John N Morelli,et al.  The issues and tentative solutions for contrast-enhanced magnetic resonance imaging at ultra-high field strength. , 2014, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[38]  Peter Caravan,et al.  Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium- and manganese-based T1 contrast agents. , 2009, Contrast media & molecular imaging.

[39]  Jan Grimm,et al.  Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging. , 2009, Small.

[40]  Sophie Laurent,et al.  Classification and basic properties of contrast agents for magnetic resonance imaging. , 2009, Contrast media & molecular imaging.

[41]  Kai Yang,et al.  In vivo pharmacokinetics, long-term biodistribution and toxicology study of functionalized upconversion nanoparticles in mice. , 2011, Nanomedicine.

[42]  J. Cheon,et al.  Chemical Design of Nanoparticle Probes for High-Performance Magnetic Resonance Imaging , 2008 .

[43]  Taeghwan Hyeon,et al.  Inorganic Nanoparticles for MRI Contrast Agents , 2009 .