title: Polymersomes conjugated to 83-14 monoclonal antibodies: in vitro targeting of brain capillary endothelial cells.
abstract: The blood-brain barrier (BBB) remains an obstacle for many drugs to reach the brain. A strategy to cross the BBB is to modify nanocarrier systems with ligands that bind to endogenous receptors expressed at the BBB to induce receptor-mediated transport. The aim of the present study was to investigate the potential of polymersomes composed of the amphiphilic diblock copolymer poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline), PDMS-b-PMOXA, for active targeting of brain capillary endothelial cells. We conjugated PDMS-b-PMOXA polymersomes to the anti-human insulin receptor antibody 83-14 and studied their uptake by brain capillary endothelial cells. Transmission electron micrography and light scattering measurements revealed the self-assembly of the block copolymers into 200 nm vesicles after extrusion. Fluorescence correlation spectroscopy was employed to calculate the number of antibodies coupled to one polymersome. Binding and uptake of the polymersomes conjugated to 83-14 mAb were studied in the human BBB in vitro model hCMEC/D3 expressing the human insulin receptor. Competitive inhibition with an excess of free 83-14 mAb demonstrated the specificity of cellular binding and uptake. Our results suggest that PDMS-b-PMOXA polymersomes conjugated to 83-14 mAb may be suitable nanocarriers for drug delivery to the brain.
authors.affiliation: Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland.
authors.forename: Le-Ha
authors.initials: LH
authors.lastname: Dieu
authors.affiliation: Department of Chemistry, University of Basel, Basel, Switzerland.
authors.forename: Dalin
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Chemistry, University of Basel, Basel, Switzerland.
authors.forename: Cornelia G
authors.initials: CG
authors.lastname: Palivan
authors.affiliation: Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland.
authors.forename: Vimalkumar
authors.initials: V
authors.lastname: Balasubramanian
authors.affiliation: Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland. Electronic address: Joerg.Huwyler@unibas.com.
authors.forename: Jörg
authors.initials: J
authors.lastname: Huwyler
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000378:metabolism; D001921:Brain / Q000098:blood supply*; D002461:Cell Line, Transformed; D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D011108:Polymers / Q000737:chemistry*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D011108:Polymers
keywords: Active targeting; Anti-human insulin receptor antibody 83-14; Blood–brain barrier; Insulin receptor; PDMS-b-PMOXA diblock copolymers; Polymersomes