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

Seras-Franzoso, J., Peebo, K., Corchero, J.L., Tsimbouri, P.M. , Unzueta, U., Rinas, U., Dalby, M.J. , Vazquez, E., García-Fruitós, E. and Villaverde, A. (2013) A nanostructured bacterial bioscaffold for the sustained bottom-up delivery of protein drugs. Nanomedicine, 8(10), pp. 1587-1599. (doi: 10.2217/nnm.12.188)

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.<p></p> Materials and 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.<p></p> Conclusions: 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.<p></p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tsimbouri, Dr Monica and Dalby, Professor Matthew
• Authors: Seras-Franzoso, J., Peebo, K., Corchero, J.L., Tsimbouri, P.M., Unzueta, U., Rinas, U., Dalby, M.J., Vazquez, E., García-Fruitós, E., and Villaverde, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Nanomedicine
• Publisher: Future Medicine
• ISSN: 1743-5889
• ISSN (Online): 1748-6963|
• Published Online: 08 February 2013