Membrane interaction of pegylated superparamagnetic nanoparticles

Iron oxide core-shell nanoparticles are gaining ever increasing interest for separation and imaging in biotechnology and biomedicine1,2, due to supposed low cytotoxicity and their superparamagnetic properties. Hydrophilic polymer-coated nanoparticles are believed to have low nonspecific interactions in biological systems, but much additional work in-vitro and in-vivo is needed to understand their detailed interactions with proteins, membranes and cells. We investigated monodisperse (SD\u3c5%), single-crystalline and superparamagnetic magnetite nanoparticles of different core size and densely grafted with poly(ethylene glycol) (Mw=5kDa), with particular emphasis on their interaction with biological membranes. Membrane interactions will determine nonspecific recognition and uptake by cells. These nanoparticles demonstrated no cytotoxicity and low cell uptake in in-vitro culture of HeLa and HEK cell lines. However, using Quartz Crystal Microbalance (QCM) a strong DLVO-type interaction could be demonstrated with anionic membranes that simulate eukaryote membranes. This interaction was only present in nonphysiological buffer with low ionic strength. Only low, weak and transient binding was observed to zwiterionic phosphocholine membranes. Core size seems to have an effect, with the smallest core size (3.3nm) yielding the strongest interactions while 8nm cores displayed almost no interaction. These results imply that dense polymer grafting and nanoparticle curvature are crucial parameters to control interactions between biomedical core-shell nanoparticles and their biomolecular environment, in particular cell membranes. The interaction between nanoparticle and membrane was furthermore shown to not perturb membrane structure by Differential Scanning Calorimetry (DSC). Please click Additional Files below to see the full abstract

Fluorescent Magnetopolymersomes: A Theranostic Platform to Track Intracellular Delivery

We present a potential theranostic delivery platform based on the amphiphilic diblock copolymer polybutadiene-block-poly (ethylene oxide) combining covalent fluorescent labeling and membrane incorporation of superparamagnetic iron oxide nanoparticles for multimodal imaging. A simple self-assembly and labeling approach to create the fluorescent and magnetic vesicles is described. Cell uptake of the densely PEGylated polymer vesicles could be altered by surface modifications that vary surface charge and accessibility of the membrane active species. Cell uptake and cytotoxicity were evaluated by confocal microscopy, transmission electron microscopy, iron content and metabolic assays, utilizing multimodal tracking of membrane fluorophores and nanoparticles. Cationic functionalization of vesicles promoted endocytotic uptake. In particular, incorporation of cationic lipids in the polymersome membrane yielded tremendously increased uptake of polymersomes and magnetopolymersomes without increase in cytotoxicity. Ultrastructure investigations showed that cationic magnetopolymersomes disintegrated upon hydrolysis, including the dissolution of incorporated iron oxide nanoparticles. The presented platform could find future use in theranostic multimodal imaging in vivo and magnetically triggered delivery by incorporation of thermorepsonsive amphiphiles that can break the membrane integrity upon magnetic heating via the embedded superparamagnetic nanoparticles

Isolation of Glucocardiolipins from Geobacillus stearothermophilus NRS 2004/3a

Glucose-substituted cardiolipins account for about 4 mol% of total phospholipid extracted from exponentially grown cells of Geobacillus stearothermophilus NRS 2004/3a. Individual glucocardiolipin species exhibited differences in fatty acid substitution, with iso-C(15:0) and anteiso-C(17:0) prevailing. The compounds were purified to homogeneity by a novel protocol and precharacterized by matrix-assisted laser desorption ionization time-of-flight mass spectrometry

N-Acetylmuramic Acid as Capping Element of �-D-Fucose-containing S-layer Glycoprotein Glycans from Geobacillus tepidamans GS5-97T

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Biocompatible Glyconanoparticles by Grafting of Sophorolipid Monolayers on Monodisperse Iron Oxide Nanoparticles

International audienceThis work presents synthesis and characterization of sophorolipid-coated monodisperse iron oxide nanoparticles. Sophorolipids are biological glycosylated amphiphiles produced by the yeast S. bombicola. In their open acidic form, sophorolipids have been used as surface stabilizing agent for metal and metal oxide nanoparticles but with poor control over size and structural properties. In this work, the COOH function of sophorolipids (SL) was modified with nitrodopamine (NDA), a catechol known for its high affinity to iron ions. The resulting new form of sophorolipid-nitrodopamide (SL-NDA) was used as surface ligand for monodisperse iron oxide nanoparticles. We show, by a combination of thermogravimetric analysis and small angle X-ray and neutron scattering, that iron oxide nanoparticles (IONP) are stabilized by a single, high-density SL-NDA layer, which results in excellent colloidal stability under biologically relevant conditions such as high protein and salt concentration. The IONP grafted with SL-NDA showed negligible uptake and no cytotoxicity tested on two representative cell lines. Thus, they reveal the potential of sophorolipids as stable and non-toxic surface coatings for IONP-based biomedical and biotechnological applications

Individually Stabilized, Superparamagnetic Nanoparticles with Controlled Shell and Size Leading to Exceptional Stealth Properties and High Relaxivities

Superparamagnetic iron oxide nanoparticles (SPION) have received immense interest for biomedical applications, with the first clinical application as negative contrast agent in magnetic resonance imaging (MRI). However, the first generation MRI contrast agents with dextran-enwrapped, polydisperse iron oxide nanoparticle clusters are limited to imaging of the liver and spleen; this is related to their poor colloidal stability in biological media and inability to evade clearance by the reticulo­endothelial system. We investigate the qualitatively different performance of a new generation of individually PEG-grafted core–shell SPION in terms of relaxivity and cell uptake and compare them to benchmark iron oxide contrast agents. These PEG-grafted SPION uniquely enable relaxivity measurements in aqueous suspension without aggregation even at 9.4 T magnetic fields due to their extraordinary colloidal stability. This allows for determination of the size-dependent scaling of relaxivity, which is shown to follow a <i>d</i>² dependence for identical core–shell structures. The here introduced core–shell SPION with ∼15 nm core diameter yield a higher <i>R</i>₂ relaxivity than previous clinically used contrast agents as well as previous generations of individually stabilized SPION. The colloidal stability extends to control over evasion of macrophage clearance and stimulated uptake by SPION functionalized with protein ligands, which is a key requirement for targeted MRI