Ultrasmall Mixed Ferrite Colloids as Multidimensional Magnetic Resonance Imaging, Cell Labeling, and Cell Sorting Agents

Abstract

One area that has been overlooked in the evolution of magnetic nanoparticle technology is the possibility of introducing informational atoms into the iron oxide core of the coated colloid. Introduction of suitable atoms into the iron oxide core offers an opportunity to produce a quantifiable probe, thereby adding one or more dimensions to the magnetic colloid's informational status. Lanthanide-doped iron oxide nanoparticles have been synthesized to introduce informational atoms through the formation of colloidal mixed ferrites. These colloids are designated ultrasmall mixed ferrite iron oxides (USMIOs). USMIOs containing 5 mol % europium exhibit superparamagnetic behavior with an induced magnetization of 56 emu/g Fe at 1.5 T, a powder X-ray diffraction pattern congruent with magnetite, and R1 and R2 relaxivity values of 15.4 (mM s) (-1) and 33.9 (mM s) (-1), respectively, in aqueous solution at 37 degrees C and 0.47 T. USMIO can be detected by five physical methods, combining the magnetic resonance imaging (MRI) qualities of iron with the sensitive and quantitative detection of lanthanide metals by neutron activation analysis (NA), time-resolved fluorescence (TRF), X-ray fluorescence, along with detection by electron microscopy (EM). In addition to quantitative detection using neutron activation analysis, the presence of lanthanides in the iron oxide matrix confers attractive optical properties for long-term multilabeling studies with europium and terbium. These USMIOs offer high photostability, a narrow emission band, and a broad absorption band combining the high sensitivity of time-resolved fluorescence with the high spatial resolution of MRI. USMIO nanoparticles are prepared through modifications of traditional magnetite-based iron oxide colloid synthetic methods. A 5 mol % substitution of ferric iron with trivalent europium yielded a colloid with nearly identical magnetic, physical, and chemical characteristics to its magnetite colloid parent.

Functionalized Nanomaterials

“…In some cases, the SPIO nanoparticles can be functionalized simply by doping some other metal ions during the preparation process. Groman et al (2007) fabricated one new mixed ferrite colloidal magnetic iron oxides by adding informational atoms (Lanthanide) during formation of the iron oxides core. The new functionalized nanoparticles, not only can be visualized by iron-based MRI, but also can be quantized by neutron activation (Eu, Sm, La, Tb add) and even visualized histologically using time resolved fluorescence (Eu, Tb added).…”

“…Josephson et al (Josephson et al 1999) crosslinked dextran with epichlohydrin, then amination was used to induce amino groups on SPIO particles. Finally, particles were functionalized by tat peptide and fluorochrome for imaging cells (Groman et al 2007;Josephson et al 1999;Koch et al 2003).…”

Magnetic Nanomaterials asMRIContrast Agents

“…Other polymers and copolymers, which have been used to coat magnetic nanoparticles, include PVP) [111 -113] , polyethylenimine ( PEI ) [114] , polyvinyl alcohol ( PVA ) [115 -117] , polysodium -4 -styrene sulfonate [118] , poly(trimethylammonium ethylacrylate methyl sulfate) -poly -(acrylamide) [119] , polyvinylbenzyl -O -beta -D -galactopyranosyl -D -gluconamide (PVLA) [120] , polycaprolactone [121] , and gummic acid [122] . In addition, several stable and biocompatible magnetic fl uids have been prepared by coating magnetic nanoparticles with proteins, such as human serum albumin ( HSA ) [123] , avidin [124] , and Annexin A5 (anxA5) -VSOP [125] .…”

Cell Tracking Using Nanoparticles

“…The nanoparticles (BioPAL, Worcester, MA, USA) first described by Groman et al [4] and used in this report have many of these characteristics. These nanoparticles are built on a nonradioactive (stableisotope) core of metals (lanthanides/iron) combined with biocompatible polymers providing low toxicity.…”

“…Cell tracking is becoming increasingly important for the successful development of regenerative therapies for the following reasons: (1) the number of cells retained at the target organ (the effective dose) in contrast to the administered number of cells can be precisely measured; (2) the cells that migrate from the injection site to other regions in the body can be imaged and quantified; (3) cell tracking aids in guiding cell delivery, in optimizing delivery protocols, and in comparing delivery technologies; (4) comparisons of the retention of different cell types at the target site become possible; (5) cell tracking helps to advance new technologies for improving therapeutic cell retention at the delivery site; and (6) cell tracking can be used to train and certify operators of cell delivery devices. This report describes a new class of nanoparticles that have the capability to both quantify and image labeled cells in vivo.…”