title: Protein A Functionalized Polyelectrolyte Microcapsules as a Universal Platform for Enhanced Targeting of Cell Surface Receptors.
abstract: Targeted delivery systems recognizing specific receptors are a key element in personalized medicine. Such systems allow the delivery of therapeutics to desired sites of the body, increasing their local concentration and thus reducing the side effects. In this study, we fabricate chemically cross-linked (PAH/PAA)2microcapsules coated with specific cell-targeting antibodies in random (via direct covalent coupling to the surface) or optimized (via supporting layer of protein A) orientation. We use these antibody-functionalized capsules to target major histocompatibility complex (MHC) class I receptors in living cells and quantify the efficiency of targeting by flow cytometry. We show for the first time the selective binding of polyelectrolyte microcapsules to MHC class I receptors, and confirm that targeting is allotype-specific. Remarkably, protein A assisted immobilization of antibodies enhances targeting efficiency by 40-50% over capsules with randomly attached antibodies. Moreover, biofunctionalized capsules reveal low levels of cytotoxicity and nonspecific binding, excluding the need of additional modification with poly(ethylene glycol). Thus, protein A coated (PAH/PAA)2microcapsules represent a unique example of universal targeting tools providing high potential for selective binding to a broad range of cell surface receptors.
authors.affiliation: Jacobs University Bremen gGmbH , Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Tatiana A
authors.identifier: http://orcid.org/0000-0002-3409-0812
authors.initials: TA
authors.lastname: Kolesnikova
authors.affiliation: Jacobs University Bremen gGmbH , Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Gayane
authors.initials: G
authors.lastname: Kiragosyan
authors.affiliation: Jacobs University Bremen gGmbH , Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Trang H N
authors.initials: TH
authors.lastname: Le
authors.affiliation: Jacobs University Bremen gGmbH , Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Springer
authors.affiliation: Jacobs University Bremen gGmbH , Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Winterhalter
mesh_terms: D002214:Capsules; D004337:Drug Carriers; D000071228:Polyelectrolytes / Q000737:chemistry*; D011956:Receptors, Cell Surface; D013205:Staphylococcal Protein A
chemical_list: D002214:Capsules; D004337:Drug Carriers; D000071228:Polyelectrolytes; D011956:Receptors, Cell Surface; D013205:Staphylococcal Protein A
keywords: MHC class I protein; antibody−antigen interaction; layer-by-layer; polyelectrolyte microcapsules; protein A; selective targeting