Researchers from the Biomolecular Nanotechnology Group at CIC biomaGUNE, led by Dr. Aitziber L. Cortajarena, have developed a simple, versatile, modular strategy for designing custom multifunctional protein hybrid nanomaterials for biotechnological and biomedical applications. Their work has been published in Chemical Science, a journal of the Royal Society of Chemistry.

The development of new nanotechnological tools for application in biomedicine is still an ongoing research goal addressed using different methodological approaches. In this context, the specific targeting of disease-related pathways and molecules, mostly proteins, is a promising strategy. While highly specific proteins are extremely useful tools for different applications, they nevertheless have certain limitations that hamper their use in some cases. Protein-based hybrid nanomaterials have recently emerged as promising platforms for manufacturing tailor-made multifunctional biological tools.

This study 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 remodelling. 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. It 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.

https://pubs.rsc.org/en/content/articlelanding/2021/SC/D0SC05215A#!divAbstract