Impact of surface coating and particle size on the uptake of small and ultrasmall superparamagnetic iron oxide nanoparticles by macrophages

Abstract

Purpose: Magnetic resonance imaging (MRI) using contrast agents like superparamagnetic iron oxide (SPIO) is an extremely versatile technique to diagnose diseases and to monitor treatment. This study tested the relative importance of particle size and surface coating for the optimization of MRI contrast and labeling efficiency of macrophages migrating to remote inflammation sites. Materials and methods:We tested four SPIO and ultrasmall superparamagnetic iron oxide (USPIO), alkali-treated dextran magnetite (ATDM) with particle sizes of 28 and 74 nm, and carboxymethyl dextran magnetite (CMDM) with particle sizes of 28 and 72 nm. Mouse macrophage RAW264 cells were incubated with SPIOs and USPIOs, and the labeling efficiency of the cells was determined by the percentage of Berlin blue-stained cells and by measuring T 2 relaxation times with 11.7-T MRI. We used trypan blue staining to measure cell viability. Results: Analysis of the properties of the nanoparticles revealed that ATDM-coated 74 nm particles have a lower T 2 relaxation time than the others, translating into a higher ability of MRI negative contrast agent. Among the other three candidates, CMDM-coated particles showed the highest T 2 relaxation time once internalized by macrophages. Regarding labeling efficiency, ATDM coating resulted in a cellular uptake higher than CMDM coating, independent of nanoparticle size. None of these particle formulations affected macrophage viability. Conclusion: This study suggests that coating is more critical than size to optimize the SPIO labeling of macrophages. Among the formulations tested in this study, the best MRI contrast and labeling efficiency are expected with ATDM-coated 74 nm nanoparticles.

Vascular and plaque imaging with ultrasmall superparamagnetic particles of iron oxide

“…Phagocytosis and receptor-mediated endocytosis are important for uptake of larger particles, whilst smaller particles are internalized by pinocytosis. Although the avidity of macrophage uptake is strongly influenced by particle size and charge, the surface coating is particularly important [ 8 , 9 ]. As a result of their smaller size, USPIOs are less readily recognized by phagocytic cells and persist in the circulation for longer than other iron particles (plasma half-life 14–30 h in humans) [ 10 , 11 ].…”

Polymer-brush-afforded SPIO Nanoparticles Show a Unique Biodistribution and MR Imaging Contrast in Mouse Organs

“… 11 There are so many studies on the improvement of the specificity of SPIO to expand their use in biomedical applications. 9 , 10 The new SPIO we used in this study showed a transient decrease of signal intensity in the liver and blood vessels, and we found no accumulation of the new SPIO in lymphatic tissues ( Figs. 1 , 2 ).…”

“…Many previous studies have aimed to improve the unique physicochemical and biological properties of SPIO by modifying particle structure, size and coating. 8 , 9 In order to improve the properties for the applications such as drug targeting and tissue or organ imaging other than liver, it is extremely important to avoid the nonspecific uptake of SPIO by peripheral macrophages as well as by MPS and RES, which could increase the half-life of the particles in the blood. 10 , 11 Ohno et al reported that their synthetic technique renders the ferric oxide particle stealthy: only very limited amounts are absorbed by phagocytes.…”

Preferential Macrophage Recruitment and Polarization in LPS-Induced Animal Model for COPD: Noninvasive Tracking Using MRI

“…To enable their enhanced detection using noninvasive MRI, macrophages labeling was performed using amine-modified PEGylated dextran-coated iron oxide nanoparticles that were checked for biocompatibility before their in vivo administration. It is well known that the size and the surface charge of SPIO nanoparticles govern cellular internalization and their distribution [24] , [25] . In line with previous studies [20] , [26] , the SPIO nanoparticles with an overall size in the range of 100 nm allowed better internalization with optimal biocompatibility in this study.…”