Zwitterionic polymer ligands: An ideal surface coating to totally suppress protein-nanoparticle corona formation?

Manon Debayle (1) , Elie Balloul (2) , Fatimata Dembele (1) , Xiangzhen Xu (1) , Mohamed Hanafi (3) , François Ribot (4) , Cornelia Monzel (2) , Mathieu Coppey (2) , Alexandra Fragola (1) , Maxime Dahan (5) , Thomas Pons (1) , Nicolas Lequeux (1)

1 LPEM - Laboratoire de Physique et d'Etude des Matériaux (UMR 8213)
2 PCC - Laboratoire Physico-Chimie Curie [Institut Curie]
3 SIMM - Sciences et Ingénierie de la Matière Molle (UMR 7615)
4 LCMCP-NANO - Novel Advanced Nano-Objects
5 LKB (Jussieu) - Laboratoire Kastler Brossel

In the last few years, zwitterionic polymers have been developed as antifouling surface coatings. However, their ability to completely suppress protein adsorption at the surface of nanoparticles in complex biological media remains undemonstrated. Here we investigate the formation of hard (irreversible) and soft (reversible) protein corona around model nanoparticles (NPs) coated with sulfobetaine (SB), phosphorylcholine (PC) and carboxybetaine (CB) polymer ligands in model albumin solutions and in whole serum. We show for the first time a complete absence of protein corona around SB-coated NPs, while PC-and CB-coated NPs undergo reversible adsorption or partial aggregation. These dramatic differences cannot be described by naïve hard/soft acid/base electrostatic interactions. Single NP tracking in the cytoplasm of live cells corroborate these in vitro observations. Finally, while modification of SB polymers with additional charged groups lead to consequent protein adsorption, addition of small neutral targeting moieties preserves antifouling and enable efficient intracellular targeting.

Mots clés: nanoparticle; protein corona; zwitterion

Domaines: Matériaux; Polymères

Manon Debayle, Elie Balloul, Fatimata Dembele, Xiangzhen Xu, Mohamed Hanafi, et al.. Zwitterionic polymer ligands: An ideal surface coating to totally suppress protein-nanoparticle corona formation?. Biomaterials, 2019, 219, pp.119357. ⟨10.1016/j.biomaterials.2019.119357⟩. ⟨hal-02189463⟩