@article{10902/29871,
year = {2023},
url = {https://hdl.handle.net/10902/29871},
abstract = {As the population ages, an epidemic of neurodegenerative diseases with devastating social consequences is looming. To address the pathologies leading to amyloid-related dementia, novel therapeutic strategies must be developed for the treatment or prevention of neural protein-folding disorders. Nanotechnology will be crucial to this scenario, especially in the design of nanoscale systems carrying therapeutic compounds that can navigate the nervous system and identify amyloid to treat it in situ. In this line, we have recently designed a highly simplified and versatile nanorobot consisting of a protein coating based on the heat shock protein 90 (Hsp90) chaperone that not only propels nanoparticles using ATP but also endows them with the extraordinary ability to fold and restore the activity of heat-denatured proteins. Here, we assess the effectiveness of these nanosystems in inhibiting/reducing the aggregation of amyloidogenic proteins. Using Raman spectroscopy, we qualitatively and quantitatively analyze amyloid by identifying and semi-quantifying the Amide I band. Our findings indicate that the coupling of Hsp90 to nanoparticles results in a more potent inhibition of amyloid formation when compared to the soluble protein. We propose that this enhanced performance may be attributed to enhanced release-capture cycles of amyloid precursor oligomers by Hsp90 molecules nearby on the nanosurface. Intelligent biocompatible coatings, like the one described here, that enhance the diffusivity and self-propulsion of nanoparticles while enabling them to carry out critical functions such as environmental scanning, identification, and amyloid prevention, present an exceptional opportunity for the development of advanced nanodevices in biomedical applications. This approach, which combined active biomolecules with synthetic materials, is poised to reveal remarkable prospects in the field of nanomedicine and biotechnology.},
organization = {ACKNOWLEDGMENTS: The authors acknowledge the financial support from the Spanish Instituto de Salud Carlos iii co-funded by the European Regional Development Fund, “Investing in your future” under projects ref. PI22/00030 and PI19/00349, and grant TED2021-129248B-I00 funded by MCIN/AEI/ 10.13039/501100011033 and by the “European Union NextGeneration EU/PRTR”. We also thank the Gobierno Regional de Cantabria and IDIVAL for the project refs IDI 20/22, INNVAL 21/19, and PREVAL 19/04 fellowship to A.R.R. and technological and administrative services. We are grateful to Dr. L García-Hevia for reading the manuscript.},
publisher = {American Chemical Society},
publisher = {ACS Chemical Neuroscience,  2023, 14, 2811-2817},
title = {Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticles},
author = {Rodríguez Ramos, Ana and González, Jesús A. and López Fanarraga, Mónica},
}