Co‐precipitation of DEAE‐dextran coated SPIONs: how synthesis conditions affect particle properties, stem cell labelling and MR contrast

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as contrast agents for stem cell tracking using magnetic resonance imaging (MRI). The total mass of iron oxide that can be internalised into cells without altering their viability or phenotype is an important criterion for the generation of contrast, with SPIONs designed for efficient labelling of stem cells allowing for an increased sensitivity of detection. Although changes in the ratio of polymer and iron salts in co-precipitation reactions are known to affect the physicochemical properties of SPIONs, particularly core size, the effects of these synthesis conditions on stem cell labelling and magnetic resonance (MR) contrast have not been established. Here, we synthesised a series of cationic SPIONs with very similar hydrodynamic diameters and surface charges, but different polymer content. We have investigated how the amount of polymer in the co-precipitation reaction affects core size and modulates not only the magnetic properties of the SPIONs but also their uptake into stem cells. SPIONs with the largest core size and lowest polymer content presented the highest magnetisation and relaxivity. These particles also had the greatest uptake efficiency without any deleterious effect on either the viability or function of the stem cells. However, for all particles internalised in cells, the T and T relaxivity was independent of the SPION's core size. Our results indicate that the relative mass of iron taken up by cells is the major determinant of MR contrast generation and suggest that the extent of SPION uptake can be regulated by the amount of polymer used in co-precipitation reactions. Copyright © 2016 John Wiley & Sons, Ltd.

Functionalized superparamagnetic iron oxide nanoparticles provide highly efficient iron-labeling in macrophages for magnetic resonance–based detection in vivo

“…The three particles had a neutral surface charge (Dex), a positive surface charge (DEAE-Dex 4:1) or a negative surface charge (CM-Dex) [20] and were incubated with BMDMs for 24 h over a range of concentrations (0–100 µg/mL). Dex and CM-Dex caused significant reductions in cell viability at 75 µg/mL (59% and 65%, respectively) and 100 µg/mL (50% and 54%, respectively) as determined by the ATP assay.…”

In vivo fate of free and encapsulated iron oxide nanoparticles after injection of labelled stem cells

“…Encapsulation of SPIONs resulted in a drop in solution relaxivity due to hindered access to the solution water protons and is similar to the previous findings of the entrapment of free particles inside the lysosomes. 20,22,32 Cell labelling efficiency and toxicity of SPIONs mMSCs were chosen for this study because they are similar to human bone marrow derived mMSCs which are being used in clinical trials, 41,42 and it has already been shown that these cells uptake free SPIONs and other nanoparticle probes with good efficacy. 12,22 To evaluate the cell labelling efficiency and toxicity of free and encapsulated SPIONs, cells were labelled with suspensions of particles (encapsulated or free) having comparable Fe content.…”

“…16 Appropriate MRI contrast agents 17,18 for cell tracking include superparamagnetic iron oxide nanoparticles (SPIONs) which generate a negative contrast. 11,[19][20][21][22][23][24] The uptake efficiency of SPIONs is strongly influenced by their functionalization. 21,25 Recently, positively-charged DEAE (diethylaminoethyl)-dextran coated SPIONs have been synthesized for enhanced cellular uptake and MRI contrast.…”

“…21,25 Recently, positively-charged DEAE (diethylaminoethyl)-dextran coated SPIONs have been synthesized for enhanced cellular uptake and MRI contrast. 20,22 Upon cell uptake, the clustering and confinement of these particles in endosomal and lysosomal compartments affects their abilities to alter the relaxation rate and hence relaxivity of the surrounding water molecules. 26,27 The critical parameter for imaging is the contrast obtained after cell labelling rather than the solution relaxivity of the particles.…”

“…26,27 The critical parameter for imaging is the contrast obtained after cell labelling rather than the solution relaxivity of the particles. 20,22 One potential approach to enhance SPIONs uptake by cells, is to assemble them inside polymeric capsules resulting in the packing of large amount of individual nanoparticles within a confined volume. [28][29][30] Polyelectrolyte multilayered (PEM) and multifunctional capsules are fabricated by layer-by-layer (LbL) assembly of oppositely charged polymeric layers around a template.…”