2 research outputs found
Biocompatible Peptide-Coated Ultrasmall Superparamagnetic Iron Oxide Nanoparticles for <i>In Vivo</i> Contrast-Enhanced Magnetic Resonance Imaging
The biocompatibility and performance
of reagents for <i>in vivo</i> contrast-enhanced magnetic
resonance imaging (MRI) are essential for their translation to the
clinic. The quality of the surface coating of nanoparticle-based MRI
contrast agents, such as ultrasmall superparamagnetic iron oxide nanoparticles
(USPIONs), is critical to ensure high colloidal stability in biological
environments, improved magnetic performance, and dispersion in circulatory
fluids and tissues. Herein, we report the design of a library of 21
peptides and ligands and identify highly stable self-assembled monolayers
on the USPIONsâ surface. A total of 86 different peptide-coated
USPIONs are prepared and selected using several stringent criteria,
such as stability against electrolyte-induced aggregation in physiological
conditions, prevention of nonspecific binding to cells, and absence
of cellular toxicity and contrast-enhanced <i>in vivo</i> MRI. The bisphosphorylated peptide 2PG-S*VVVT-PEG4-ol provides the
highest biocompatibility and performance for USPIONs, with no detectable
toxicity or adhesion to live cells. The 2PG-S*VVVT-PEG4-ol-coated
USPIONs show enhanced magnetic resonance properties, <i>r</i><sub>1</sub> (2.4 mM<sup>â1</sup>·s<sup>â1</sup>) and <i>r</i><sub>2</sub> (217.8 mM<sup>â1</sup>·s<sup>â1</sup>) relaxivities, and greater <i>r</i><sub>2</sub>/<i>r</i><sub>1</sub> relaxivity ratios (>90)
when compared to those of commercially available MRI contrast agents.
Furthermore, we demonstrate the utility of 2PG-S*VVVT-PEG4-ol-coated
USPIONs as a <i>T</i><sub>2</sub> contrast agent for <i>in vivo</i> MRI applications. High contrast enhancement of the
liver is achieved as well as detection of liver tumors, with significant
improvement of the contrast-to-noise ratio of tumor-to-liver contrast.
It is envisaged that the reported peptide-coated USPIONs have the
potential to allow for the specific targeting of tumors and hence
early detection of cancer by MRI
Design and Synthesis of Polymer-Functionalized NIR Fluorescent DyesâMagnetic Nanoparticles for Bioimaging
The fluorescent probes having complete spectral separation between absorption and emission spectra (large Stokes shift) are highly useful for solar concentrators and bioimaging. In bioimaging application, NIR fluorescent dyes have a greater advantage in tissue penetration depth compared to visible-emitting organic dyes or inorganic quantum dots. Here we report the design, synthesis, and characterization of an amphiphilic polymer, poly(isobutylene-<i>alt</i>-maleic anhyride)-functionalized near-infrared (NIR) IR-820 dye and its conjugates with iron oxide (Fe<sub>3</sub>O<sub>4</sub>) magnetic nanoparticles (MNPs) for optical and magnetic resonance (MR) imaging. Our results demonstrate that the Stokes shift of unmodified dye can be tuned (from âŒ106 to 208 nm) by the functionalization of the dye with polymer and MNPs. The fabrication of bimodal probes involves (i) the synthesis of NIR fluorescent dye (IR-820 cyanine) functionalized with ethylenediamine linker in high yield, >90%, (ii) polymer conjugation to the functionalized NIR fluorescent dye, and (iii) grafting the polymer-conjugated dyes on iron oxide MNPs. The resulting uniform, small-sized (<i>ca</i>. 6 nm) NIR fluorescent dyeâmagnetic hybrid nanoparticles (NPs) exhibit a wider emissive range (800â1000 nm) and minimal cytotoxicity. Our preliminary studies demonstrate the potential utility of these NPs in bioimaging by means of direct labeling of cancerous HeLa cells <i>via</i> NIR fluorescence microscopy and good negative contrast enhancement in <i>T</i><sub>2</sub>-weighted MR imaging of a murine model