title: Bacteriomimetic invasin-functionalized nanocarriers for intracellular delivery.
abstract: Intracellular bacteria invade mammalian cells to establish an infectious niche. The current work models adhesion and subsequent internalization strategy of pathogenic bacteria into mammalian cells to design a bacteriomimetic bioinvasive delivery system. We report on the surface functionalization of liposomes with a C-terminal fragment of invasin (InvA497), an invasion factor in the outer membrane of Yersinia pseudotuberculosis. InvA497-functionalized liposomes adhere to mammalian epithelial HEp-2 cell line at different infection stages with a significantly higher efficiency than liposomes functionalized with bovine serum albumin. Covalent attachment of InvA497 results in higher cellular adhesion than liposomes with physically adsorbed InvA497 with non-specific surface protein alignment. Uptake studies in HEp-2 cells indicate active internalization of InvA497-functionalized liposomes via β1-integrin receptor-mediated uptake mechanism mimicking the natural invasion strategy of Y. pseudotuberculosis. Uptake studies in Caco-2 cells at different polarization states demonstrate specific targeting of the InvA497-functionalized liposomes to less polarized cells reflecting the status of inflamed cells. Moreover, when loaded with the anti-infective agent gentamicin and applied to HEp-2 cells infected with Y. pseudotuberculosis, InvA497-functionalized liposomes are able to significantly reduce the infection load relative to non-functionalized drug-loaded liposomes. This indicates a promising application of such a bacteriomimetic system for drug delivery to intracellular compartments.
authors.affiliation: Dept. of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Campus A4 1, D-66123 Saarbrücken, Germany; Department of Pharmaceutics, Alexandria University, Alexandria 21521, Egypt.
authors.forename: Hagar Ibrahim
authors.initials: HI
authors.lastname: Labouta
authors.affiliation: Dept. of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Campus A4 1, D-66123 Saarbrücken, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Menina
authors.affiliation: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Kochut
authors.affiliation: Dept. of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Campus A4 1, D-66123 Saarbrücken, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Geyer
authors.affiliation: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Dersch
authors.affiliation: Dept. of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Campus A4 1, D-66123 Saarbrücken, Germany; Department of Pharmacy, Saarland University, D-66123 Saarbrücken, Germany. Electronic address: Claus-Michael.Lehr@helmholtz-hzi.de.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001422:Bacterial Adhesion; D058491:Bacterial Load / Q000187:drug effects; D001692:Biological Transport; D032701:Biomimetics; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D004337:Drug Carriers; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D005839:Gentamicins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D019012:Integrin beta1; D007700:Kinetics; D008081:Liposomes; D053758:Nanoparticles; D036103:Nanotechnology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D015011:Yersinia pseudotuberculosis / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D005839:Gentamicins; D019012:Integrin beta1; D008081:Liposomes; D010446:Peptide Fragments; C053476:invasin, Yersinia
keywords: Bacteriomimetic liposomes; Bioinvasive carriers; Cell uptake kinetics; Intracellular delivery; Receptor competition experiments