Nanohybridization as a Route to a Water-Friendly Therapeutic Tool for Rescuing Misfolded Proteins
Misfolded proteins cause several threatening pathologies, ranging from Alzheimer’s disease to cystic fibrosis. Although several protein folding correctors were tested, their delivery is usually inadequate. Here, via a self-assembly wet reaction, colloidal γ-Fe2O3 was used to immobilize two correctors (C4 and C17) for a cystic fibrosis-associated transmembrane protein. The as-obtained core–shell magnetic nanohybrids were extensively characterized, revealing high drug loading and remarkable chemical stability in water. In addition, a dedicated computational study revealed that the whole organic multilayer is involved in a long-range polarization on the nanoconjugate surface, showing sufficient colloidal stability for its application in cells and in contrast with the cargo’s hydrophobic nature. Experiments conducted in HEK293 cells, expressing a mutated subunit of α-sarcoglycan, showed a positive effect on protein complex recovery. This study represents the first in vitro example of a multifunctional nanochaperone for the structural recovery of misfolded proteins.
Authors
- Graziano Rilievo (ORCID: https://orcid.org/0000-0003-4098-5636)
- Lavinia Rutigliano (ORCID: https://orcid.org/0000-0002-3482-3553)
- Marcello Carotti (ORCID: https://orcid.org/0000-0002-7742-339X)
- Simone Molinari (ORCID: https://orcid.org/0000-0003-4105-4833)
- Massimiliano Magro (ORCID: https://orcid.org/0000-0002-4644-004X)
- Barbara Fresch (ORCID: https://orcid.org/0000-0002-0988-0644)
- Dorianna Sandonà (ORCID: https://orcid.org/0000-0002-9908-2442)
- Juri Ugolotti (ORCID: https://orcid.org/0000-0003-2971-1415)
- Roberta Sacchetto (ORCID: https://orcid.org/0000-0001-8884-8302)
- Fábio Vianello (ORCID: https://orcid.org/0000-0002-4874-7205)
- Lucio Litti (ORCID: https://orcid.org/0000-0001-6247-5456)
- Federica Tonolo (ORCID: https://orcid.org/0000-0002-7780-8994)
- Alessandro Cecconello (ORCID: https://orcid.org/0000-0002-7075-2801)
- Tiziana Martinello (ORCID: https://orcid.org/0000-0002-5949-6261)
- Aura Cencini (ORCID: https://orcid.org/0009-0004-1830-9062)
- Mary Bortoluzzi (ORCID: https://orcid.org/0009-0008-4573-6931)
Institutions
- University of Padua (IT)
- Regional Centre of Advanced Technologies and Materials (CZ)
- Istituto Pasteur (IT)
- University of Bari Aldo Moro (IT)
- Palacký University Olomouc (CZ)
- University of Brescia (IT)
Publication Details
- Journal
- ACS Nanoscience Au
- Published
- 2025-11-07
- DOI
- https://doi.org/10.1021/acsnanoscienceau.5c00119
- Primary Topic
- Nanoparticle-Based Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.00