Core-Shell Chaperones: Zwitterionic core-shell NPs as protein stabilisers

Proteins are powerful medicines and industrial tools, but to be used as such, they require a correctly folded structure. During large-scale production, many proteins misfold and aggregate into inactive forms, dramatically increasing costs and limiting their use in biotechnology and medicine. Nature solves this problem with molecular chaperones—specialized helpers that stabilize proteins and guide them back into their functional shapes. This project aims to develop artificial, reusable versions of such chaperones using nanotechnology. We will study core–shell nanoparticles with a magnetic core and a soft outer shell composed of zwitterionic polymers—materials that strongly bind water and interact gently with proteins. Binding to these polymer shells will be designed to prevent protein aggregation and promote correct folding. By systematically tuning polymer length, density, and chemistry, the project seeks to identify the key design rules that determine whether proteins remain stable, misfold, or can be rescued once aggregated. A unique feature of the approach is the magnetic nanoparticle core. It allows artificial chaperones to be recovered and reused and enables localized heating via alternating magnetic fields. This controlled nanoscale heating is expected to help break apart amyloid-like protein aggregates, while the polymer shell simultaneously stabilizes the released proteins and promotes correct refolding. Using well-defined model, but medically and industrially relevant, proteins, the project combines physical chemistry, nanomaterials synthesis, and biophysics to establish quantitative links between protein–nanoparticle interactions and functional outcomes. If successful, this work could reduce the cost of protein manufacturing, improve the stability of protein drugs, and inspire new strategies to counter harmful protein aggregation in biotechnology and biomedical contexts.