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6 results on '"Kooijmans, Sander"'

1. The fluid membrane determines mechanics of erythrocyte extracellular vesicles and is softened in hereditary spherocytosis.

Author

Vorselen D, van Dommelen SM, Sorkin R, Piontek MC, Schiller J, Döpp ST, Kooijmans SAA, van Oirschot BA, Versluijs BA, Bierings MB, van Wijk R, Schiffelers RM, Wuite GJL, and Roos WH

Subjects
Erythrocyte Membrane metabolism, Erythrocytes metabolism, Extracellular Vesicles metabolism, Humans, Membrane Fluidity, Microscopy, Atomic Force, Proteins metabolism, Erythrocyte Membrane chemistry, Erythrocytes chemistry, Extracellular Vesicles chemistry, Spherocytosis, Hereditary metabolism
Abstract

Extracellular vesicles (EVs) are widely studied regarding their role in cell-to-cell communication and disease, as well as for applications as biomarkers or drug delivery vehicles. EVs contain membrane and intraluminal proteins, affecting their structure and thereby likely their functioning. Here, we use atomic force microscopy for mechanical characterization of erythrocyte, or red blood cell (RBC), EVs from healthy individuals and from patients with hereditary spherocytosis (HS) due to ankyrin deficiency. While these EVs are packed with proteins, their response to indentation resembles that of fluid liposomes lacking proteins. The bending modulus of RBC EVs of healthy donors is ~15 k b T, similar to the RBC membrane. Surprisingly, whereas RBCs become more rigid in HS, patient EVs have a significantly (~40%) lower bending modulus than donor EVs. These results shed light on the mechanism and effects of EV budding and might explain the reported increase in vesiculation of RBCs in HS patients.

Published
2018
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2. Exploring interactions between extracellular vesicles and cells for innovative drug delivery system design

Author

Kooijmans, Sander, de Jong, Olivier G., Schiffelers, Raymond, Afd Pharmaceutics, Pharmaceutics, Afd Pharmaceutics, and Pharmaceutics

Subjects
Biocompatibility, RNA delivery, Pharmaceutical Science, 02 engineering and technology, Exosomes, Extracellular vesicles, Small Molecule Libraries, Synthetic drugs, Extracellular Vesicles, 03 medical and health sciences, Drug Delivery Systems, Extracellular vesicle surface, Humans, Uptake mechanisms, 030304 developmental biology, Drug Carriers, 0303 health sciences, Chemistry, Effector, Protein delivery, Small molecules, 021001 nanoscience & nanotechnology, Small molecule, Microvesicles, Cell biology, Reporter systems, Drug Design, Drug delivery, 0210 nano-technology
Abstract

Extracellular vesicles (EVs) are submicron cell-secreted structures containing proteins, nucleic acids and lipids. EVs can functionally transfer these cargoes from one cell to another to modulate physiological and pathological processes. Due to their presumed biocompatibility and capacity to circumvent canonical delivery barriers encountered by synthetic drug delivery systems, EVs have attracted considerable interest as drug delivery vehicles. However, it is unclear which mechanisms and molecules orchestrate EV-mediated cargo delivery to recipient cells. Here, we review how EV properties have been exploited to improve the efficacy of small molecule drugs. Furthermore, we explore which EV surface molecules could be directly or indirectly involved in EV-mediated cargo transfer to recipient cells and discuss the cellular reporter systems with which such transfer can be studied. Finally, we elaborate on currently identified cellular processes involved in EV cargo delivery. Through these topics, we provide insights in critical effectors in the EV-cell interface which may be exploited in nature-inspired drug delivery strategies.

Published
2021

3. A post-insertion strategy for surface functionalization of bacterial and mammalian cell-derived extracellular vesicles

Author

Jiang, Linglei, Luirink, Joen, Kooijmans, Sander A A, van Kessel, Kok P M, Jong, Wouter, van Essen, Max, Seinen, Cor W, de Maat, Steven, de Jong, Olivier G, Gitz-François, Jerney F F, Hennink, Wim E, Vader, Pieter, Schiffelers, Raymond M, Pharmaceutics, Afd Pharmaceutics, Molecular Microbiology, AIMMS, LaserLaB - Molecular Biophysics, Pharmaceutics, and Afd Pharmaceutics

Subjects
Surface Properties, Blotting, Western, Biophysics, Cell Culture Techniques, Outer membrane vesicles, 02 engineering and technology, Extracellular vesicles, Biochemistry, Post insertion, 03 medical and health sciences, Mice, Microscopy, Electron, Transmission, Labelling, Cell Line, Tumor, Animals, Humans, Molecular Biology, 030304 developmental biology, 0303 health sciences, Liposome, Bacteria, Chemistry, Translation (biology), 021001 nanoscience & nanotechnology, Flow Cytometry, Poly(ethylene glycol)lipids, Immunohistochemistry, Cell biology, Bacterial Outer Membrane, HEK293 Cells, Post-insertion, Nucleic acid, Surface modification, Electrophoresis, Polyacrylamide Gel, 0210 nano-technology, Drug carrier
Abstract

Extracellular vesicles (EVs) are nanoparticles which are released by cells from all three domains of life: Archaea, Bacteria and Eukarya. They can mediate cell-cell communication by transferring cargoes such as proteins and nucleic acids between cells. EVs receive great interest in both academia and industry as they have the potential to be natural drug carriers or vaccine candidates. However, limitations to their clinical translation exist as efficient isolation, loading, labelling and surface-engineering methods are lacking. In this article, we investigate a ‘post-insertion’ approach, which is commonly used in the functionalization of liposomes in the pharmaceutical field, on two different EV types: mammalian cell-derived EVs and bacteria-derived EVs. We aimed to find an easy and flexible approach to functionalize EVs, thereby improving the labelling, isolation, and surface-engineering.

Published
2021

4. Recombinant phosphatidylserine-binding nanobodies for targeting of extracellular vesicles to tumor cells: a plug-and-play approach† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7nr06966a

Author

Kooijmans, Sander A. A., Gitz-Francois, Jerney J. J. M., Schiffelers, Raymond M., and Vader, Pieter

Subjects
ErbB Receptors, Chemistry, Extracellular Vesicles, Drug Delivery Systems, HEK293 Cells, Recombinant Fusion Proteins, Antigens, Surface, Humans, Phosphatidylserines, Single-Domain Antibodies, Milk Proteins
Abstract

Decoration of isolated extracellular vesicles with recombinant phosphatidylserine-binding nanobodies increases their uptake by tumor cells., Extracellular vesicles (EVs) are increasingly being recognized as candidate drug delivery systems due to their ability to functionally transfer biological cargo between cells. However, manipulation of targeting properties of EVs through engineering of the producer cells can be challenging and time-consuming. As a novel approach to confer tumor targeting properties to isolated EVs, we generated recombinant fusion proteins of nanobodies against the epidermal growth factor receptor (EGFR) fused to phosphatidylserine (PS)-binding domains of lactadherin (C1C2). C1C2-nanobody fusion proteins were expressed in HEK293 cells and isolated from culture medium with near-complete purity as determined by SDS-PAGE. Fusion proteins specifically bound PS and showed no affinity for other common EV membrane lipids. Furthermore, C1C2 fused to anti-EGFR nanobodies (EGa1-C1C2) bound EGFR with high affinity and competed with binding of its natural ligand EGF, as opposed to C1C2 fused to non-targeting control nanobodies (R2-C1C2). Both proteins readily self-associated onto membranes of EVs derived from erythrocytes and Neuro2A cells without affecting EV size and integrity. EV-bound R2-C1C2 did not influence EV–cell interactions, whereas EV-bound EGa1-C1C2 dose-dependently enhanced specific binding and uptake of EVs by EGFR-overexpressing tumor cells. In conclusion, we developed a novel strategy to efficiently and universally confer tumor targeting properties to PS-exposing EVs after their isolation, without affecting EV characteristics, circumventing the need to modify EV-secreting cells. This strategy may also be employed to decorate EVs with other moieties, including imaging probes or therapeutic proteins.

Published
2018

5. Raman spectroscopy as a quick tool to assess purity of extracellular vesicle preparations and predict their functionality.

Author

Gualerzi, Alice, Kooijmans, Sander Alexander Antonius, Niada, Stefania, Picciolini, Silvia, Brini, Anna Teresa, Camussi, Giovanni, and Bedoni, Marzia

Subjects
*RAMAN spectroscopy, *GEL permeation chromatography, *CELL separation, *HUMAN stem cells, *BONE marrow cells, *STEM cells
Abstract

Extracellular vesicles (EVs) from a variety of stem cell sources are believed to harbour regenerative capacity, which may be exploited for therapeutic purposes. Because of EV interaction with other soluble secreted factors, EV activity may depend on the employed purification method, which limits cross-study comparisons and therapeutic development. Raman spectroscopy (RS) is a quick and easy method to assess EV purity and composition, giving in-depth biochemical overview on EV preparation. Hereby, we show how this method can be used to characterise EVs isolated from human liver stem cells and bone marrow mesenchymal stem/stromal cells by means of conventional ultracentrifugation (UC) and size exclusion chromatography (SEC) protocols. The obtained EV preparations were demonstrated to be characterised by different degrees of purity and a specific Raman fingerprint that represents both the cell source and the isolation procedure used. Moreover, RS provided useful hints to explore the factors underlying the functional diversity of EV preparations from the same cell source, thus representing a valuable tool to assess EV quality prior to functional assays or therapeutic application. [ABSTRACT FROM AUTHOR]

Published
2019
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6. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting.

Author

Kooijmans, Sander A. A., Aleza, Clara Gómez, Roffler, Steve R., van Solinge, Wouter W., Vader, Pieter, and Schiffelers, Raymond M.

Subjects
*EPIDERMAL growth factor receptors, *CANCER cells, *DRUG delivery systems
Abstract

Background: Extracellular vesicles (EVs) are attractive candidate drug delivery systems due to their ability to functionally transport biological cargo to recipient cells. However, the apparent lack of target cell specificity of exogenously administered EVs limits their therapeutic applicability. In this study, we propose a novel method to equip EVs with targeting properties, in order to improve their interaction with tumour cells. Methods: EV producing cells were transfected with vectors encoding for anti-epidermal growth factor receptor (EGFR) nanobodies, which served as targeting ligands for tumour cells, fused to glycosylphosphatidylinositol (GPI) anchor signal peptides derived from decay-accelerating factor (DAF). EVs were isolated using ultrafiltration/size-exclusion liquid chromatography and characterized using western blotting, Nanoparticle Tracking Analysis, and electron microscopy. EV-tumour cell interactions were analyzed under static conditions using flow cytometry and under flow conditions using a live-cell fluorescence microscopycoupled perfusion system. Results: EV analysis showed that GPI-linked nanobodies were successfully displayed on EV surfaces and were highly enriched in EVs compared with parent cells. Display of GPI-linked nanobodies on EVs did not alter general EV characteristics (i.e. morphology, size distribution and protein marker expression), but greatly improved EV binding to tumour cells dependent on EGFR density under static conditions. Moreover, nanobody-displaying EVs showed a significantly improved cell association to EGFR-expressing tumour cells under flow conditions. Conclusions: We show that nanobodies can be anchored on the surface of EVs via GPI, which alters their cell targeting behaviour. Furthermore, this study highlights GPI-anchoring as a new tool in the EV toolbox, which may be applied for EV display of a variety of proteins, such as antibodies, reporter proteins and signaling molecules. [ABSTRACT FROM AUTHOR]

Published
2016
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