Labouta, HI, Menina, S, Kochut, A, Gordon, S, Geyer, R, Dersch, P and Lehr, C-M (2015) Bacteriomimetic invasin-functionalized nanocarriers for intracellular delivery. Journal of Controlled Release, 220 (Pt A). pp. 414-424. ISSN 1873-4995

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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.

Item Type:	Article
Uncontrolled Keywords:	0903 Biomedical Engineering, 1115 Pharmacology And Pharmaceutical Sciences
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Divisions:	Pharmacy & Biomolecular Sciences
Publisher:	Elsevier
Related URLs:	Author
Date Deposited:	06 Jun 2017 09:21
Last Modified:	03 Aug 2022 08:25
DOI or Identification number:	10.1016/j.jconrel.2015.10.052
URI:	https://researchonline.ljmu.ac.uk/id/eprint/6632

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