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)

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Publisher's URL: http://dx.doi.org/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 Penelope 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 > Institute of Molecular Cell and Systems Biology
Journal Name:Nanomedicine
Publisher:Future Medicine
ISSN:1743-5889
ISSN (Online):1748-6963|
Published Online:08 February 2013

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