A nanostructured bacterial bioscaffold for the sustained bottom-up delivery of protein drugs

verfasst von

Joaquin Seras-Franzoso, Karl Peebo, José Luis Corchero, Penelope M. Tsimbouri, Ugutz Unzueta, Ursula Rinas, Matthew J. Dalby, Esther Vazquez, Elena García-Fruitós, Antonio Villaverde

Abstract

Aims: Bacterial inclusion bodies (IBs) are protein-based, amyloidal nanomaterials that mechanically stimulate mammalian cell proliferation upon surface decoration. However, their biological performance as potentially functional scaffolds in mammalian cell culture still needs to be explored. Materials & methods: Using fluorescent proteins, we demonstrate significant membrane penetration of surface-attached IBs and a corresponding intracellular bioavailability of the protein material. Results: When IBs are formed by protein drugs, such as the intracellular acting human chaperone Hsp70 or the extracellular/intracellular acting human FGF-2, IB components intervene on top-growing cells, namely by rescuing them from chemically induced apoptosis or by stimulating cell division under serum starvation, respectively. Protein release from IBs seems to mechanistically mimic the sustained secretion of protein hormones from amyloid-like secretory granules in higher organisms. Conclusion: We propose bacterial IBs as biomimetic nanostructured scaffolds (bioscaffolds) suitable for tissue engineering that, while acting as adhesive materials, partially disintegrate for the slow release of their biologically active building blocks. The bottom-up delivery of protein drugs mediated by bioscaffolds offers a highly promising platform for emerging applications in regenerative medicine.

Organisationseinheit(en)

Institut für Technische Chemie

Externe Organisation(en)

Centros de Investigacion Biomedica en Red - CIBER
Universidad Autónoma de Barcelona (UAB)
University of Glasgow

Typ

Artikel

Journal

Nanomedicine

Band

8

Seiten

1587-1599

Anzahl der Seiten

13

ISSN

1743-5889

Publikationsdatum

10.2013

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Bioengineering, Medizin (sonstige), Biomedizintechnik, Allgemeine Materialwissenschaften

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.2217/nnm.12.188 (Zugang: Geschlossen)