Toward Design of Magnetic Nanoparticle Clusters Stabilized by Biocompatible Diblock Copolymers for T₂-Weighted MRI Contrast

Abstract

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.

Artificial local magnetic field inhomogeneity enhances T2 relaxivity

“…On this basis, magnetic resonance switch (MRSw) systems have been developed to detect a wide range of targets, from metal ions to tumour cells272829. The T 2 relaxivity of magnetic clusters is dependent on a number of parameters such as size, frame composition and water penetrating behaviour3031. However, the underlying mechanism of the clustering effect is not clear and the attempts to generalize the principles of single-particle relaxivity to clusters have been confronted with a great deal of complications26.…”

Real-time observation of protein aggregates in pharmaceutical formulations using liquid cell electron microscopy

“…Particles in each image were individually measured across the long axis of each particle using the line measurement tool in the software package using previously described routines. 21 To validate these measurements, we performed manual measurements using the SPIDER software package 22 and automated measurements using the PARTICLE package (http://www.image-analysis.net/EM/). Data from these methods were nearly identical.…”

Recent advances in magnetic nanoparticle-based multi-modal imaging

“…2c). 15 The aggregates of magnetic nanoparticles can increase m s and, thus, achieve a higher R 2 . Feridex s , r 2 = 108 mM À1 s À1 ).…”

“…13 As the nanoparticle size increases, the m s values increase from 25 to 43, 80, and 102 emu g À1 (Fe), resulting in the increment of the T 2 relaxivity coefficient (r 2 ) up to 218 mM À1 s À1 , which is approximately 2-fold higher than that of the representative iron oxide-based T 2 MRI contrast agent (i.e. 15 For example, nanoclusters with a hydrodynamic size of 163 nm are prepared by enwrapping 7.4 nm iron oxide nanoparticles with poly(ethylene oxide-co-lactide) micelles. 14 Recently, there have been several reports to further increase the T 2 contrast effects by controlled clustering of magnetic nanoparticles to fit in the SDR.…”