TY - JOUR

T1 - A nanostructured bacterial bioscaffold for the sustained bottom-up delivery of protein drugs

AU - Seras-Franzoso, Joaquin

AU - Peebo, Karl

AU - Luis Corchero, José

AU - Tsimbouri, Penelope M.

AU - Unzueta, Ugutz

AU - Rinas, Ursula

AU - Dalby, Matthew J.

AU - Vazquez, Esther

AU - García-Fruitós, Elena

AU - Villaverde, Antonio

N1 - Funding Information: This study was funded by Modalidad Infrastructuras Científico-Tecnológicas (MINECO; BFU2010-17450), Agència de Gestió d‘Ajuts Universitaris i de Recerca (AGAUR; 2009SGR-00108) and Centro de Investigación Biomédica En Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, Spain). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. E García-Fruitós is supported by the Programa Personal de Técnico de Apoyo (Ministerio De Economia Y Competitividad). J Seras-Franzoso is recipient of a PIF doctoral fellowship from Universitat Autònoma de Barcelona, K Peebo of an Erasmus placement scholarship and A Villaverde of an ICREA ACADEMIA award. A Villaverde, E García-Fruitós and E Vazquez are coinventors of a patent (P200900045) on the use of inclusion bodies as reagents for mammalian cell culture. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

KW - biomaterial

KW - building block

KW - drug delivery

KW - scaffold

KW - tissue engineering

UR - http://www.scopus.com/inward/record.url?scp=84879634206&partnerID=8YFLogxK

U2 - 10.2217/nnm.12.188

DO - 10.2217/nnm.12.188

M3 - Article

C2 - 23394133

AN - SCOPUS:84879634206

VL - 8

SP - 1587

EP - 1599

JO - Nanomedicine

JF - Nanomedicine

SN - 1743-5889

IS - 10

ER -