PhD Thesis Defense | Thu Phuong Le

Synthesis and structural characterization of single-chain nanoparticles from polypeptides and proteins

Candidate: Thu Phuong Le

Supervisors: Prof. Arantxa Arbe and Dr. Paula Malo De Molina

Summary

Polymer nanoparticles present unprecedented opportunities in biomedicine, particularly in sensing, imaging, and drug delivery. In particular, single-chain nanoparticles (SCNPs), derived from unimolecular precursor polymers via intramolecular crosslinking, represent the smallest size limit of nanogels and exhibit unique properties that make them attractive for diverse applications. Their sparse and flexible conformations, reminiscent of those of intrinsically disordered proteins (IDPs), position SCNPs as powerful synthetic models for biological studies and as functional platforms in catalysis and drug delivery. While the SCNP synthesis has been extensively studied in synthetic polymer systems, their formation from natural polypeptides and proteins remains poorly understood. This is primarily attributed to the inherent chemical complexity and the diverse non-covalent and covalent forces involved, leading to inter- and intra-molecular interactions as well as sensitivity to external environments. Key stabilizing factors—such as hydrophobic interactions, electrostatic forces, hydrogen bonding, and disulfide linkages—are critical for maintaining structural integrity. Disrupting these delicate balances for synthesis purposes can compromise system stability and potentially lead to undesired aggregation. In this Thesis, the investigation of the synthesis and structural characterization of nanoparticles and SCNPs using polypeptides and proteins is presented, with a focus on understanding the influence of the chain conformation on the nanoparticle formation and structure.