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Engineering multifunctional metal/protein hybrid nanomaterials as tools for therapeutic intervention and high-sensitivity detection

Abstract: Protein-based hybrid nanomaterials have recently emerged as promising platforms to fabricate tailored multifunctional biologics for biotechnological and biomedical applications. This work shows a simple, modular, and versatile strategy to design custom protein hybrid nanomaterials. This approach combines for the first time the engineering of a therapeutic protein module with the engineering of a nanomaterial-stabilizing module within the same molecule, resulting in a multifunctional hybrid nanocomposite unachievable through conventional material synthesis methodologies. As the first proof of concept, a multifunctional system was designed ad hoc for the therapeutic intervention and monitoring of myocardial fibrosis. This hybrid nanomaterial combines a designed Hsp90 inhibitory domain and a metal nanocluster stabilizing module resulting in a biologic drug labelled with a metal nanocluster. The engineered nanomaterial actively reduced myocardial fibrosis and heart hypertrophy in an animal model of cardiac remodeling. In addition to the therapeutic effect, the metal nanocluster allowed for in vitro, ex vivo, and in vivo detection and imaging of the fibrotic disease under study. This study evidences the potential of combining protein engineering and protein-directed nanomaterial engineering approaches to design custom nanomaterials as theranostic tools, opening up unexplored routes to date for the next generation of advanced nanomaterials in medicine.

 Fuente: Chemical Science, 2021,12, 2480-2487

 Publisher: Royal Society of Chemistry

 Year of publication: 2021

 No. of pages: 8

 Publication type: Article

 DOI: 10.1039/d0sc05215a

 ISSN: 2041-6520,2041-6539

 Spanish project: PID2019-111649RB-I00; RTI2018-095214-B-I00; BIO2016-77367-C2-1-R; BIO2015-72124-EXP

 Publication Url: https://www.doi.org/10.1039/d0sc05215a

Authorship

AIRES, ANTONIO

LÓPEZ MARTÍNEZ, ELENA

LLARENA, IRANTZU

GERAKI, KALOTINA

SÁNCHEZ CANO, CARLOS

CORTAJARENA, AITZIBER L.