Aspherical and Spherical InvA497-Functionalized Nanocarriers for Intracellular Delivery of Anti-Infective Agents
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PURPOSE: The objective of this work was to evaluate the potential of polymeric spherical and aspherical invasive nanocarriers, loaded with antibiotic, to access and treat intracellular bacterial infections. METHODS: Aspherical nanocarriers were prepared by stretching of spherical precursors, and both aspherical and spherical nanocarriers were surface-functionalized with the invasive protein InvA497. The relative uptake of nanocarriers into HEp-2 epithelial cells was then assessed. Nanocarriers were subsequently loaded with a preparation of the non-permeable antibiotic gentamicin, and tested for their ability to treat HEp-2 cells infected with the enteroinvasive bacterium Shigella flexneri. RESULTS: InvA497-functionalized nanocarriers of both spherical and aspherical shape showed a significantly improved rate and extent of uptake into HEp-2 cells in comparison to non-functionalized nanocarriers. Functionalized and antibiotic-loaded nanocarriers demonstrated a dose dependent killing of intracellular S. flexneri. A slight but significant enhancement of intracellular bacterial killing was also observed with aspherical as compared to spherical functionalized nanocarriers at the highest tested concentration. CONCLUSIONS: InvA497-functionalized, polymer-based nanocarriers were able to efficiently deliver a non-permeable antibiotic across host cell membranes to affect killing of intracellular bacteria. Functionalized nanocarriers with an aspherical shape showed an interesting future potential for intracellular infection therapy.
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Surface functionalization with InvA497 is beneficial for enhancing both in vitro cell uptake and antimicrobial efficacy of polymeric nanoparticles.
“This group has shown that surface functionalization with InvA497 is beneficial for enhancing both in vitro cell uptake and antimicrobial efficacy of polymeric nanoparticles 69 .”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [69]
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Nanotechnology approaches for global infectious diseases
Kirtane, A. R., Verma, M., Karandikar, P., Furin, J., Langer, R., & Traverso, G. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00866-8 · Cited by 520 · see citing works
- Authors
- Castoldi, A., Empting, M., De Rossi, C., Mayr, K., Dersch, P., Hartmann, R., Müller, R., Gordon, S., & Lehr, C.-M.
- Affiliations
- Helmholtz Centre for Infection Research (DE)
- Helmholtz Institute for Pharmaceutical Research Saarland (DE)
- Corresponding author
- Gordon, Sarah
- Venue
- Pharmaceutical Research
- Published
- 2018-12-05
- Volume
- 36
- Issue
- 1
- Pages
- 22-22
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- PMC
- PMC6290668
- OpenAlex
- W2902445771
- Cited by
- 22
- References
- 41
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 4
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Pharmaceutical Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HZI (Helmholtz Centre for Infection Research) (submittedVersion, cc-by-nc-sa)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Liverpool John Moores University (submittedVersion, cc-by)
- Funders
- Liverpool John Moores University
- 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
- polymeric nanocarriers, intracellular drug delivery, gentamicin, Shigella flexneri, intracellular bacterial infection, cellular uptake
- MeSH terms
- Anti-Bacterial Agents, Biological Transport, Cell Line, Drug Carriers, Dysentery, Bacillary, Epithelial Cells, Gentamicins, Humans, Kinetics, Liposomes, Particle Size, Shigella flexneri, Adhesins, Bacterial, Microbial Viability, Nanoparticles
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