Details
Original language | English |
---|---|
Article number | 1900849 |
Journal | Advanced Science |
Volume | 6 |
Issue number | 18 |
Early online date | 24 Jul 2019 |
Publication status | Published - 18 Sept 2019 |
Abstract
Two structurally and functionally unrelated proteins, namely Omomyc and p31, are engineered as CD44-targeted inclusion bodies produced in recombinant bacteria. In this unusual particulate form, both types of protein materials selectively penetrate and kill CD44+ tumor cells in culture, and upon local administration, promote destruction of tumoral tissue in orthotropic mouse models of human breast cancer. These findings support the concept of bacterial inclusion bodies as versatile protein materials suitable for application in chronic diseases that, like cancer, can benefit from a local slow release of therapeutic proteins.
Keywords
- biofabrication, cancer therapy, functional amyloids, inclusion bodies, protein drug release
ASJC Scopus subject areas
- Medicine(all)
- Medicine (miscellaneous)
- Chemical Engineering(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Materials Science(all)
- Engineering(all)
- Physics and Astronomy(all)
Sustainable Development Goals
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In: Advanced Science, Vol. 6, No. 18, 1900849, 18.09.2019.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Targeting Antitumoral Proteins to Breast Cancer by Local Administration of Functional Inclusion Bodies
AU - Pesarrodona, Mireia
AU - Jauset, Toni
AU - Díaz-Riascos, Zamira V.
AU - Sánchez-Chardi, Alejandro
AU - Beaulieu, Marie Eve
AU - Seras-Franzoso, Joaquin
AU - Sánchez-García, Laura
AU - Baltà-Foix, Ricardo
AU - Mancilla, Sandra
AU - Fernández, Yolanda
AU - Rinas, Ursula
AU - Schwartz, Simó
AU - Soucek, Laura
AU - Villaverde, Antonio
AU - Abasolo, Ibane
AU - Vázquez, Esther
N1 - Funding information: M.P. and T.J. contributed equally to this work. This study has been supported by La Fundació Marató TV3 and NanoCanTri (CIBER-BBN) to E.V. and I.A., and partially by ISCIII (PI15/00272 and PI1702242 co-founded by Fondo Europeo de Desarrollo Regional (FEDER), to E.V. and S.S., respectively), and Agencia Estatal de Investigación (AEI) and FEDER (BIO2016-76063-R, AEI/FEDER, UE), AGAUR (2017SGR-229) and CIBER-BBN (VENOM4CANCER) granted to A.V. Protein production and DLS have been partially performed by the ICTS “NANBIOSIS,” more specifically by the Protein Production Platform of CIBER-BBN/IBB (http://www.nanbiosis.es/unit/u1-protein-production-platform-ppp/) and the Biomaterial Processing and Nanostructuring Unit (http://www.nanbiosis.es/portfolio/u6-biomaterial-processing-and-nanostructuring-unit/), respectively. Biodistribution and immunohistochemistry assays were performed at the ICTS “NANBIOSIS,” specifically by U20/FVPR (http://www.nanbiosis.es/portfolio/u20-in-vivo-experimental-platform/). L.S.-G. was supported by predoctoral fellowship from AGAUR (2018FI_B2_00051). L.S. was supported by the European Research Council (CoG #617473) and the Instituto de Salud Carlos III (FIS #PI16/01224). J.S.-F. was supported by an AECC post-doctoral fellowship. A.V. received an ICREA ACADEMIA award.
PY - 2019/9/18
Y1 - 2019/9/18
N2 - Two structurally and functionally unrelated proteins, namely Omomyc and p31, are engineered as CD44-targeted inclusion bodies produced in recombinant bacteria. In this unusual particulate form, both types of protein materials selectively penetrate and kill CD44+ tumor cells in culture, and upon local administration, promote destruction of tumoral tissue in orthotropic mouse models of human breast cancer. These findings support the concept of bacterial inclusion bodies as versatile protein materials suitable for application in chronic diseases that, like cancer, can benefit from a local slow release of therapeutic proteins.
AB - Two structurally and functionally unrelated proteins, namely Omomyc and p31, are engineered as CD44-targeted inclusion bodies produced in recombinant bacteria. In this unusual particulate form, both types of protein materials selectively penetrate and kill CD44+ tumor cells in culture, and upon local administration, promote destruction of tumoral tissue in orthotropic mouse models of human breast cancer. These findings support the concept of bacterial inclusion bodies as versatile protein materials suitable for application in chronic diseases that, like cancer, can benefit from a local slow release of therapeutic proteins.
KW - biofabrication
KW - cancer therapy
KW - functional amyloids
KW - inclusion bodies
KW - protein drug release
UR - http://www.scopus.com/inward/record.url?scp=85069946471&partnerID=8YFLogxK
U2 - 10.1002/advs.201900849
DO - 10.1002/advs.201900849
M3 - Article
AN - SCOPUS:85069946471
VL - 6
JO - Advanced Science
JF - Advanced Science
SN - 2198-3844
IS - 18
M1 - 1900849
ER -