Hyaluronic acid presentation at the surface of self‐assembled nanoparticles transforms a hyaluronidase HYAL1 substrate into an efficient and selective inhibitor

Haohao Duan (1, 2, 3) , Mark Donovan (1) , Franck Hernandez (1) , Carmelo Di Primo (4) , Elisabeth Garanger (2, 3) , Xavier Schultze (1) , Sébastien Lecommandoux (2, 3)

1 L'Oréal Recherche - L'Oréal Recherche France
2 LCPO - Laboratoire de Chimie des Polymères Organiques
3 Team 3 LCPO : Polymer Self-Assembly & Life Sciences
4 ARN : régulations naturelle et artificielle

In this study, an original method of macromolecular design was used to develop a hyaluronidase‐1 (HYAL1) inhibitor from its principal substrate, hyaluronic acid (HA). HA‐based nanoparticles (HA‐NP) were obtained by copolymer self‐assembly and their effects on HYAL1 activity were investigated by combining different analytical tools. Compared to HA, HA‐NP exhibited an enhanced stability against HYAL1 degradation while maintaining its interaction with HA receptors CD44 and aggrecan. HA‐NP displayed a strong and selective inhibition of HYAL1 activity and retarded the hydrolysis of higher molar mass HA in solution. A co‐nanoprecipitation process was used to formulate a range of hybrid nanoparticle samples, which demonstrated the specificity and efficiency of HA‐NP in HYAL1 inhibition.

Mots clés: self-assembly; Surface plasmon resonance; block copolymer; hyaluronan; targeting; receptor inhibition; Hyaluronic acid; Hyaluronidase; Polymer nanoparticles

Domaines: Polymères; Matière Molle [cond-mat.soft]; Biochimie [q-bio.BM]

Haohao Duan, Mark Donovan, Franck Hernandez, Carmelo Di Primo, Elisabeth Garanger, et al.. Hyaluronic acid presentation at the surface of self‐assembled nanoparticles transforms a hyaluronidase HYAL1 substrate into an efficient and selective inhibitor. Angewandte Chemie International Edition, 2020, 59 (32), pp.13591-13596. ⟨10.1002/anie.202005212⟩. ⟨hal-02561770⟩