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.
Original language | English |
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Pages (from-to) | 414-424 |
Number of pages | 11 |
Journal | Journal of Controlled Release |
Volume | 220 |
Issue number | Part A |
Early online date | 29 Oct 2015 |
DOIs | |
Publication status | Published - 28 Dec 2015 |
Bibliographical note
Publisher Copyright:© 2015 Elsevier B.V.
Keywords
- Bacteriomimetic liposomes
- Bioinvasive carriers
- Cell uptake kinetics
- Intracellular delivery
- Receptor competition experiments
ASJC Scopus subject areas
- Pharmaceutical Science