Marcel De Cuyper

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Organization: Katholieke Universiteit Leuven – Campus Kortrijk
Department: Interdisciplinary Research Centre
Title:
Co-reporter:Stefaan J.H. Soenen, Uwe Himmelreich, Nele Nuytten, Marcel De Cuyper
Biomaterials 2011 32(1) pp: 195-205
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.08.075
Co-reporter:Stefaan J.H. Soenen, Alain R. Brisson, Eveline Jonckheere, Nele Nuytten, Sisareuth Tan, Uwe Himmelreich, Marcel De Cuyper
Biomaterials 2011 32(6) pp: 1748-1758
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.11.005
Co-reporter:N. Nuytten, M. Hakimhashemi, T. Ysenbaert, L. Defour, J. Trekker, S.J.H. Soenen, Paul Van der Meeren, M. De Cuyper
Colloids and Surfaces B: Biointerfaces 2010 80(2) pp: 227-231
Publication Date(Web):
DOI:10.1016/j.colsurfb.2010.06.009
Co-reporter:Stefaan J. H. Soenen MSc.;Dries Vercauteren MSc.;Kevin Braeckmans Dr.;Wim Noppe Dr.;Stefaan De Smedt .
ChemBioChem 2009 Volume 10( Issue 2) pp:257-267
Publication Date(Web):
DOI:10.1002/cbic.200800510

Abstract

Iron oxide nanocrystals that are dextran coated are widely exploited biomedically for magnetic resonance imaging (MRI), hyperthermia cancer treatment and drug or gene delivery. In this study, the use of an alternative coating consisting of a phospholipid bilayer directly attached to the magnetite core is described. The flexible nature of the magnetoliposome (ML) coat, together with the simple production procedure, allows rapid and easy modification of the coating, offering many exciting possibilities for the use of these particles in biomedical applications. Upon incubation of neutral MLs with an equimolar amount of cationic 1,2-distearoyl-3-trimethylammoniumpropane (DSTAP)-bearing vesicles, approximately one third of the cationic lipids are incorporated into the ML coat. This is in line with a theoretical model predicting transferability of only the outer leaflet phospholipids of bilayer structures. Most interestingly, the use of MLs containing 3.33 % DSTAP with a positive ζ-potential of (31.3±7.3) mV (mean ±SD) at neutral pH, results in very heavy labelling of a variety of biological cells (up to (70.39±4.52) pg of Fe per cell, depending on the cell type) without cytotoxic effects. The results suggest the general applicability of these bionanocolloids for cell labelling. Mechanistically, the nanoparticles are primarily taken up by clathrin-mediated endocytosis and follow the endosomal pathway. The fate of the ML coat after internalisation has been studied with different fluorescent lipid conjugates, which because of the unique features of the ML coat can be differentially incorporated in either the inner or the outer layer of the ML bilayer. It is shown that, ultimately, iron oxide cores surrounded by an intact lipid bilayer appear in endosomal structures. Once internalised, MLs are not actively exocytosed and remain within the cell. The lack of exocytosis and the very high initial loading of the cells by MLs result in a highly persistent label, which can be detected, even in highly proliferative 3T3 fibroblasts, for up to at least one month (equivalent to approximately 30 cell doublings), which by far exceeds any values reported in the literature.

Co-reporter:Marcel De Cuyper, Stefaan J.H. Soenen, Kenneth Coenegrachts, Léon Ter Beek
Analytical Biochemistry 2007 Volume 367(Issue 2) pp:266-273
Publication Date(Web):15 August 2007
DOI:10.1016/j.ab.2007.05.006
Small unilamellar phospholipid vesicles containing the phosphatidylethanolamine–diethylene triamine pentaacetic acid (PE–DTPA) conjugate as one of the building stones were constructed. The ability of these colloids to complex gadolinium(III) ions at the surface of both the inner and outer bilayer shells was verified using a colorimetric method with Arsenazo III as a dye indicator. On incubation of these functionalized vesicles with magnetoliposomes (MLs, nanometer-sized magnetite cores encapsulated in a phospholipid bilayer), PE–DTPA percolates into the ML coat. The PE–DTPA content could be fine-tuned by varying the conjugate concentration in the donor vesicles. In the experimental conditions applied, up to 500 Gd3+ ions were immobilized per ML colloid. The resulting ML–Gd3+ complexes might have great potential, for example, as a novel magnetic resonance imaging contrast agent.
Co-reporter:Stefaan J. H. Soenen Drs.;Johan Baert
ChemBioChem 2007 Volume 8(Issue 17) pp:
Publication Date(Web):17 OCT 2007
DOI:10.1002/cbic.200700327

A comparative study that deals with the internalisation of different types of magnetoliposomes (MLs) by 3T3 fibroblasts revealed that cationic MLs proved to be superior to neutral and anionic ones. Internalisation was visualised both by optical light and transmission electron microscopy. The latter showed that the cationic MLs ultimately ended up in lysosomal structures. The effect of increasing 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) concentrations in the cationic ML coat has been elucidated. High uptake efficiency was only achieved with MLs that carry a high DOTAP payload. However, these structures also demonstrated toxic effects. The use of the saturated distearoyl analogue (DSTAP) at identical concentrations led to improved uptake efficiency and lower toxicity. By using iron-oxide-free vesicles, it was shown that the toxicity was due to lipid bilayer constituents and not the iron oxide. In conclusion, the use of DMPC–DSTAP (96.67:3.33; molar ratio) MLs results in an extremely high labelling of 3T3 fibroblasts with iron oxides (47.66 pg Fe per cell) without evoking any influence on cell viability.

Co-reporter:S.J. Soenen, N. Nuytten, S.C. De Smedt, M. De Cuyper
Drug Discovery Today (December 2010) Volume 15(Issues 23–24) pp:1081-1082
Publication Date(Web):1 December 2010
DOI:10.1016/j.drudis.2010.09.358
Co-reporter:S.J. Soenen, N. Nuytten, U. Himmelreich, M. De Cuyper
Drug Discovery Today (December 2010) Volume 15(Issues 23–24) pp:
Publication Date(Web):1 December 2010
DOI:10.1016/j.drudis.2010.09.359
Co-reporter:Stefaan J.H. Soenen, Eszter Illyes, Dries Vercauteren, Kevin Braeckmans, Zsuzsa Majer, Stefaan C. De Smedt, Marcel De Cuyper
Biomaterials (December 2009) Volume 30(Issue 36) pp:
Publication Date(Web):1 December 2009
DOI:10.1016/j.biomaterials.2009.08.050
Magnetoliposomes (MLs), built up of ultrasmall iron oxide cores each individually surrounded by a lipid bilayer, have emerged as highly biocompatible nanoparticles and promising tools in many biomedical applications. To improve cell uptake, cationic amphiphiles are inserted into the ML coat, but this often induces cytotoxic effects. In the present work, we synthesized and tested a cationic peptide–lipid conjugate (dipalmitoylphosphatidylethanolamine-succinyl-tetralysine [DPPE-succ-(Lys)4]) which is entirely composed of biodegradable moieties and specifically designed to exert minimal cytotoxic effects. Uptake studies with both murine 3T3 fibroblasts and C17.2 neural progenitor cells shows 95.63 ± 5.83 pg Fe and 87.46 ± 5.62 pg Fe per cell after 24 h, respectively, for 16.66% DPPE-succ-(Lys)4-containing MLs, with no effect on cell viability. However, these high intracellular nanoparticle concentrations transiently affect actin cytoskeleton architecture, formation of focal adhesion complexes and cell proliferation, returning to control levels after approximately 7 days post ML-incubation in both cell types. This study points out the great need for thorough characterization of cell–nanoparticle interactions as subtle time-dependent effects are hard to monitor and commonly used viability and functionality assays are not sufficient to address the broad spectrum of possible interferences of the nanoparticle with normal cell functioning.