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.
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InvA497-functionalized gentamycin-loaded liposomes caused a 30% reduction in bacterial load in an in vitro model of Y. pseudotuberculosis infection, whereas albumin-functionalized liposomes had no effect.
“InvA497-funtionalized gentamycin-loaded liposomes caused a 30% reduction in bacterial load in an in vitro model of Y. pseudotuberculosis infection, whereas albumin-functionalized liposomes had no effect 68 .”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [68]
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- Authors
- Labouta, H. I., Menina, S., Kochut, A., Gordon, S., Geyer, R., Dersch, P., & Lehr, C.-M.
- Affiliations
- Helmholtz Centre for Infection Research (DE)
- Corresponding author
- Lehr, Claus-Michael
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 220
- Issue
- Pt A
- Pages
- 414-424
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2199978910
- Cited by
- 29
- References
- 45
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 1 · 2016: 3
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Liverpool John Moores University (acceptedVersion)
- HZI (Helmholtz Centre for Infection Research) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- invasin, liposomes, intracellular drug delivery, Yersinia pseudotuberculosis, epithelial cell adhesion, cell polarization, HEp-2 cells, Caco-2 cells
- MeSH terms
- Anti-Bacterial Agents, Bacterial Adhesion, Biological Transport, Cell Membrane, Drug Carriers, Epithelial Cells, Gentamicins, Humans, Kinetics, Liposomes, Peptide Fragments, Yersinia pseudotuberculosis, Adhesins, Bacterial, Caco-2 Cells, Integrin beta1, Biomimetics, Nanotechnology, Nanoparticles, Bacterial Load
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