Aspherical and spherical InvA497-functionalized nanocarriers for intracellular delivery of anti-infective agents

Arianna Castoldi, Martin Empting, Chiara De Rossi, Karsten Mayr, Petra Dersch, Rolf Hartmann, Rolf Müller, Sarah Gordon, Claus Michael Lehr

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number22
Number of pages13
JournalPharmaceutical Research
Volume36
Issue number1
Early online date5 Dec 2018
DOIs
Publication statusPublished - 2019

Bibliographical note

Funding Information:
The authors thank Dr. Cristiane de Souza Carvalho Wodarz for her advice and assistance with the bacterial efficacy studies. Dr. Sabrina Muehlen and Carina Schmühl are gratefully acknowledged for support and training related to bacterial culture and invasion protocols. Tanja Krause is also acknowledged for the InvA497 purification. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Publisher Copyright:
© 2018, The Author(s).

Keywords

  • AOT-gentamicin
  • aspherical nanoparticles
  • bacteriomimetic nanocarriers
  • intracellular infection
  • invasin

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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