Water-soluble derivatives of gadolinium-containing metallofullerenes have been considered to be excellent candidates for new magnetic resonance imaging (MRI) contrast agents because of their high relaxivity and characteristic encapsulation of the lanthanide ions (Gd(3+)), preventing their release into the bioenvironment. The trimetallic nitride template endohedral metallofullerenes (TNT EMFs) have further advantages of high stability, high relative yield, and encapsulation of three Gd(3+) ions per molecule as illustrated by the previously reported nearly spherical, Gd3N@I(h)-C80. In this study, we report the preparation and functionalization of a lower-symmetry EMF, Gd3N@C(s)-C84, with a pentalene (fused pentagons) motif and an egg-shaped structure. The Gd3N@C84 derivative exhibits a higher (1)H MR relaxivity compared to that of the Gd3N@C80 derivative synthesized the same way, at low (0.47 T), medium (1.4 T), and high (9.4 T) magnetic fields. The Gd3N@C(s)-C84 derivative exhibits a higher hydroxyl content and aggregate size, as confirmed by X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS) experiments, which could be the main reasons for the higher relaxivity.
Magnetic Block Ionomer Clusters (MBIClusters) with hydrophilic ionic cores and nonionic coronas have been prepared that have ultrahigh transverse NMR relaxivities together with capacities for incorporating high concentrations of polar antibiotic payloads. Magnetite-polymer nanoparticles were assembled by adsorbing the polyacrylate block of an aminofunctional poly(ethylene oxide-b-acrylate) (H2N-PEO-b-PAA) copolymer onto magnetite nanoparticles. The PEO blocks extended into aqueous media to keep the nanoparticles dispersed. Amines at the tips of the H2N-PEO corona were then linked through reaction with a PEO diacrylate oligomer to yield MBIClusters where the metal oxide in the precursor nanoparticles were distinctly separated by the hydrophilic polymer. The intensity average spacing between the magnetite nanoparticles within the clusters was estimated to be ~50 nm. These MBIClusters with hydrophilic intra-cluster space had transverse relaxivities (r2’s) that increased from 190 to 604 s−1 mM Fe−1 measured at 1.4 T and 37 °C as their average sizes increased. The clusters were loaded with up to ~38 wt% of the multi-cationic drug gentamicin. MRI scans focused on the livers of mice demonstrated that these MBIClusters are sensitive contrast agents.
Magnetic nanoparticles coated with polymers have existing and further potential for applications in medicine, including magnetic resonance imaging (MRI) imaging for diagnostics and assessing biodistribution, and their capacity to remotely generate heat in response to alternating current magnetic fields to elicit biological responses. Advances in such domains rely on developing better understanding of how such materials respond to magnetic fields. This paper reports thermosensitive properties of poly(N-isopropylacrylamide-co-Nile Red)-coated magnetic nanostructures upon passing through the lower critical solution temperature (LCST) of the polymer brush, and correlation of this behavior with formation of aggregates. Discrete magnetite nanoparticles coated with brush layers comprised of terminally attached poly(N-isopropylacrylamide-co-Nile Red) afforded highly water-dispersible nanoparticles (intensity average diameter of 38 nm) with good colloidal stability in phosphate buffers. The nanoparticles displayed enhanced transverse (T 2 ) NMR relaxometric behavior as the temperature was increased through the LCST. Moreover, incorporation of the environmentally sensitive Nile Red dye into the copolymer leads to significant changes in fluorescence emission intensity upon aggregation that present new possibilities for the remote fluorescence detection of aggregated structures.
We report the fabrication of magnetic particles comprised of clusters of iron oxide nanoparticles, 7.4 nm mean diameter, stabilized by a biocompatible, amphiphilic diblock copolymer, poly(ethylene oxide-b-D,L-lactide). Particles with quantitative incorporation of up to 40 wt % iron oxide and hydrodynamic sizes in the range of 80-170 nm were prepared. The particles consist of hydrophobically modified iron oxide nanoparticles within the core-forming polylactide block with the poly(ethylene oxide) forming a corona to afford aqueous dispersibility. The transverse relaxivities (r2) increased with average particle size and exceeded 200 s(-1) mM Fe(-1) at 1.4 T and 37 °C for iron oxide loadings above 30 wt %. These experimental relaxivities typically agreed to within 15% with the values predicted using analytical models of transverse relaxivity and cluster (particle core) size distributions derived from cryo-TEM measurements. Our results show that the theoretical models can be used for the rational design of biocompatible MRI contrast agents with tailored compositions and size distributions.
Magnetic block ionomer complexes (MBICs) containing a combination of therapeutic and imaging agents are of great interest for delivering drugs and tracking their biodistribution with magnetic resonance imaging. With an aim to develop nanocarriers with high drug loadings that integrate magnetic nanoparticles into one system, we herein report antibiotic-laden MBICs based on assembly of poly(ethylene oxide-b-acrylate) (PEO-b-PAA) ionomers with nanomagnetite and gentamicin. The polymer was bound to the magnetic nanoparticle surfaces via ligand adsorption of the PAA block, thereby creating a double corona structure with a nonionic PEO shell and an ionic region rich in PAA. The portion of carboxylates that were not bound to the magnetite provided binding sites for drug loading via ionic complexation. PEO was chosen as a block copolymer segment to improve biocompatibility and aid in dispersion through interparticle steric repulsion. Intensity average diameters increased from 34 to 62 nm upon adding the drug, suggesting that the particles formed small clusters. Zeta potentials decreased from approximately −40 without gentamicin to approximately −10 mV with the drug, indicating that the drug effectively localized the charges in the MBIC cores. Approximately 35 wt % of the encapsulated gentamicin was released under physiological conditions within 10 h, and this was followed by slower release of another 7% by 18 h. The solid magnetite core serves as a multifunctional substrate for block ionomers to stably adsorb, thus acting as a pseudo-crosslinking site in the complexes that enhances their stability. Complexes between PEO-b-PAA and gentamicin without magnetite instantaneously dissociate in saline buffer. When the same copolymer was adsorbed onto magnetite, subsequent complexation with gentamicin resulted in stable complexes that withstood media with physiological ionic strength.
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