Facile non-hydrothermal synthesis of oligosaccharide coated sub-5 nm magnetic iron oxide nanoparticles with dual MRI contrast enhancement effects

Abstract

Ultrafine sub-5 nm magnetic iron oxide nanoparticles coated with oligosaccharides (SIO) with dual T1-T2 weighted contrast enhancing effect and fast clearance has been developed as magnetic resonance imaging (MRI) contrast agent. Excellent water solubility, biocompatibility and high stability of such sub-5 nm SIO nanoparticles were achieved by using the “in-situ polymerization” coating method, which enables glucose forming oligosaccharides directly on the surface of hydrophobic iron oxide nanocrystals. Reported ultrafine SIO nanoparticles exhibit a longitudinal relaxivity (r1) of 4.1 mM−1s−1 and a r1/r2 ratio of 0.25 at 3 T (clinical field strength), rendering improved T1 or “brighter” contrast enhancement in T1-weighted MRI in addition to typical T2 or “darkening” contrast of conventional iron oxide nanoparticles. Such dual contrast effect can be demonstrated in liver imaging with T2 “darkening” contrast in the liver parenchyma but T1 “bright” contrast in the hepatic vasculature. More importantly, this new class of ultrafine sub-5 nm iron oxide nanoparticles showed much faster body clearance than those with larger sizes, promising better safety for clinical applications.

Magnetic Nanoparticles for Precision Oncology: Theranostic Magnetic Iron Oxide Nanoparticles for Image-Guided and Targeted Cancer Therapy

“…When the nanoparticle core size is smaller (<5 nm), the T 2 contrast or darkening effect is reduced, while the effect on longitudinal relaxation time, or T 1 contrast, becomes more prominent. Thus, T 1 signal is dominated and gives rise to bright T 1 MRI contrast as demonstrated in vitro and in vivo by sub-5-nm core size ultrafine IONPs reported by Huang et al [18]. Understanding the interplay between T 1 and T 2 contrast at different core sizes, one can use ultrashort echo time MRI sequence to obtain bright T 1 contrasts with larger sized IONPs as demonstrated in the study in which the accumulation of 10-nm core size IONPs can be observed with ultrashort TE MRI with bright T 1 contrast in orthotopic pancreatic tumors following systemic delivery [55].…”

“…It is generally agreed that nanoparticles at diameters ranging from 10 to 100 nm are optimal for in vivo applications with acceptable pharmacokinetics. IONP sizes developed by different groups are all within the optimized size range for in vivo delivery [18,41,42] (Figure 2). Ultrasmall IONPs with core size (<10 nm) and ultrafine IONPs (<5 nm) have been synthesized and characterized [18,43].…”

“…IONP sizes developed by different groups are all within the optimized size range for in vivo delivery [18,41,42] (Figure 2). Ultrasmall IONPs with core size (<10 nm) and ultrafine IONPs (<5 nm) have been synthesized and characterized [18,43]. Those small IONPs are promising IONPs because they can be excreted from the kidneys for body clearance.…”

“…Significant discoveries have been made in the production of IONPs with different core sizes, surface functions, MRI contrast properties and drug-loading capacity [15,17]. For example, various surface modifications have been developed to reduce nonspecific uptake of IONPs by macrophages in the reticuloendothelial system, such as polyethylene glycol (PEG) or antifouling polymer coating for altering the surface properties of IONPs [18,19]. Additionally, shape of nanoparticles also affects blood half-life, macrophage uptake, extravasation and internalization of nanoparticles by cells [20,21].…”

“…A marked feature of future science group MNPs for precision oncology: theranostic magnetic IONPs for image-guided & targeted cancer therapy Review magnetic IONPs is the ability of the production of controlled and uniform core size nanoparticles with a size-dependent magnetization. Ultrafine IONPs at a sub-5-nm core size have been developed for improved delivery efficiency and dual MRI contrast [14,18]. Such small-size IONPs can be efficiently delivered into tumors through the enhanced permeability and retention effect mediated by the leaking tumor vasculatures [22,23].…”