PEGylation of surfacted magnetite core–shell nanoparticles for biomedical application

Abstract

Corresponding authors: E. Illés (illese@chem.hu) and E. Tombácz (tombacz@chem.u-szeged.hu) Elsevier ECIS2013 Best Poster Prize awarded contribution Present address: A. Jedlovszky-Hajdú, Laboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary. Graphical abstract Highlights• The mechanisms of oleate adsorption on as-synthesized and purified MNPs are different.• PEG adsorption increases the weight of steric component in electrosteric stabilization by oleate.• MNPs become clustered upon OA adsorption; cluster size is larger for as-synthesized MNPs.• PEG-surfacted MNPs do not show cytotoxicity and hemolytic potential on human blood.• MRI T2 enhancement of as-synthesized MNPs supports higher degree of clustering. AbstractThe surface of oleate double layer coated (surfacted) magnetite nanoparticles (OA@MNPs) was coated by PEG (poly(ethylene glycol) of Mw=1000, 4000 or 20000 Da, respectively, to get core-shell structured nanomagnets. The oleate bilayers were prepared in two different ways; (i) oleic acid was added directly into the magnetite co-precipitation mixture containing the MNPs to obtain OA@s-MNP samples -s-MNP standing for "as-synthesized MNP" and (ii) sodium oleate (oleate anion, OA) was added to the purified MNPs to obtain OA@p-MNP samples -p-MNP standing for "purified MNP". The effect of the surfactant addition method on the pH-and ionic strength-dependent stability (dynamic laser light scattering and laser-Doppler electrophoresis experiments), the biomedical applicability (MRI measurements) and the biocompatibility (blood sedimentation and blood smear tests) of the coreshell MNPs was studied. Different mechanisms of oleate adsorption were found in ATR FT-IR experiments (inner sphere surface complexation via ligand exchange for the s-MNPs and additional H-bonding for the p-MNPs), suggesting different behaviour. The colloidal stability and salt tolerance of the two kinds of OA@MNPs were similar, but the hydrodynamic diameter of the OA@s-MNP was considerably larger than that of OA@p-MNP. In accordance with this, the r2 relaxation was also higher for the s-MNP samples (~400 and ~ 200 mM -1 s -1 , respectively). The physico-chemical tests indicate that the OA-coated MNPs form clusters and the degree of clustering of OA@s-MNPs is significantly 2 greater than that of OA@p-MPNs. PEGylation does not appear to affect colloidal stability and salt tolerance meaningfully. The adsorption of PEG was proved experimentally. We have found that the PEG top layer decreases the electrostatic contribution, nevertheless increases the steric contribution of the original electrosteric stabilization caused by the OA double layer. However, an increase in the molecular weight above 1000 Da and the amount of added PEG above 5 mmol/g gradually reduces the salt tolerance of the samples. The results indicate strong potential for biomedical application and biocompatibility of the PEGylated MNPs.

Hemocompatibility and Biomedical Potential of Poly(Gallic Acid) Coated Iron Oxide Nanoparticles for Theranostic Use

“…The morphological analysis of human blood cells showed neither deformation nor decomposition of RBCs in the presence of PGA coated nanoparticles. As it is seen in Figure 3, no aggregation of RBCs was detected revealing excellent hemocompatibility of PGA@MNPs comparable to that of other polyacid- [22,27], polyethylehene oxide (PEG)- [23] and The effect of PGA@MNP on viability of white blood cells (WBCs) was tested by measuring the viability factor (WVF) and the results obtained for the blood of Donor #3 are demonstrated in Figure 4. The viable fraction of WBCs of EDTA-coagulated native blood decreased from 0.99 to 0.97 after 240 minutes, which is a spontaneous process in in vitro experiments.…”

“…The high transverse relaxivity of PGA@MNP is probably due the strong hydration of the highly negatively charged PGA shell near the magnetite core. The enhanced relaxation of large amount of protons near the MNP surface leads to the decrease in signal intensity and increase in the negative contrast [23]. The r 2 relaxivity of PGA@MNPs ∼387 mM -1 s -1 is somewhat lower than that of naked MNPs (measured at pH ∼4 as 429.5 ± 9.5 mM -1 s -1 [34]).…”

“…The MRI contrast enhancement efficiency of the PGA@MNP was studied by determining the T 1 (longitudinal) and T 2 (transversal) relaxation times and calculating r 1 and r 2 relaxivities as described in our previously published paper [23] by using a clinical MRI instrument GE Excite HDxt (GE Medical Systems, Milwaukee, WI) at magnetic field strength of 1.5 T. The contrast enhancement of coated particles was measured using the standard "birdcage" head coil. The MNP dispersions were prepared at nominal Fe concentrations of 0.009, 0.018, 0.045, 0.09, 0.135, 0.18 and 0.22 mM and the exact iron content of the samples was measured by inductively coupled plasma (ICP) method using an Optima 7000 DV ICP-OES instrument (PerkinElmer, Shelton, CT, USA).…”

“…The longitudinal and transverse relaxivity values (r 1 and r 2 , respectively) were calculated by plotting the relaxation rates (R 1 =1/T 1 and R 2 =1/T 2 ) against the Fe concentration as described in our previous papers [23,34]. According to our expectations, small r 1 value (1.8 mM ) was obtained for PGA@MNP, which is characteristic for superparamagnetic iron oxide nanoparticles (SPION) in general [23]. However, remarkable T 2 contrast enhancement was recorded for the PGA coated MNPs, shown in Figure 7 as the concentration dependence of the R 2 relaxation rate.…”

Controlled clustering of carboxylated SPIONs through polyethylenimine

“…The most advanced approach is to combine diagnostics and therapy (theranostics) making clinical applications more efficient. The surface of magnetite nanoparticles (MNPs) has to be coated to prevent aggregation at physiological conditions (neutral pH, high electrolyte concentration) [6][7][8][9]. Metal-oxide surfaces are believed to form complexes with molecules having carboxylic moieties such as carboxylated polyelectrolytes (PE) that are a good choice for covering the surface [10][11][12][13].…”