Opsonisation of nanoparticles prepared from poly(β-hydroxybutyrate) and poly(trimethylene carbonate)-b-poly(malic acid) amphiphilic diblock copolymers: Impact on the in vitro cell uptake by primary human macrophages and HepaRG hepatoma cells

E. Vene (1) , G. Barouti (2) , K. Jarnouen (1) , T. Gicquel (1, 3) , C. Rauch (1) , C. Ribault (1) , Sophie M. Guillaume (2) , S. Cammas-Marion (2) , P. Loyer (1)

1 Foie, métabolismes et cancer
2 ISCR - Institut des Sciences Chimiques de Rennes
3 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]

The present work reports the investigation of the biocompatibility, opsonisation and cell uptake by human primary macrophages and HepaRG cells of nanoparticles (NPs) formulated from poly(β-malic acid)-b-poly(β-hydroxybutyrate) (PMLA-b-PHB) and poly(β-malic acid)-b-poly(trimethylene carbonate) (PMLA-b-PTMC) diblock copolymers, namely PMLA800-b-PHB7300, PMLA4500-b-PHB4400, PMLA2500-b-PTMC2800 and PMLA4300-b-PTMC1400. NPs derived from PMLA-b-PHB and PMLA-b-PTMC do not trigger lactate dehydrogenase release and do not activate the secretion of pro-inflammatory cytokines demonstrating the excellent biocompatibility of these copolymers derived nano-objects. Using a protein adsorption assay, we demonstrate that the binding of plasma proteins is very low for PMLA-b-PHB-based nano-objects, and higher for those prepared from PMLA-b-PTMC copolymers. Moreover, a more efficient uptake by macrophages and HepaRG cells is observed for NPs formulated from PMLA-b-PHB copolymers compared to that of PMLA-b-PTMC-based NPs. Interestingly, the uptake in HepaRG cells of NPs formulated from PMLA800-b-PHB7300 is much higher than that of NPs based on PMLA4500-b-PHB4400. In addition, the cell internalization of PMLA800-b-PHB7300 based-NPs, probably through endocytosis, is strongly increased by serum pre-coating in HepaRG cells but not in macrophages. Together, these data strongly suggest that the binding of a specific subset of plasmatic proteins onto the PMLA800-b-PHB7300-based NPs favors the HepaRG cell uptake while reducing that of macrophages.

Mots clés: Poly(trimethylene carbonate); Poly(hydroxy alkanoate); Poly(malic acid); Nanoparticle; Macrophages; HepaRG cells

Domaines: Sciences pharmaceutiques; Chimie thérapeutique

E. Vene, G. Barouti, K. Jarnouen, T. Gicquel, C. Rauch, et al.. Opsonisation of nanoparticles prepared from poly(β-hydroxybutyrate) and poly(trimethylene carbonate)-b-poly(malic acid) amphiphilic diblock copolymers: Impact on the in vitro cell uptake by primary human macrophages and HepaRG hepatoma cells. International Journal of Pharmaceutics, 2016, 513 (1-2), pp.438--452. ⟨10.1016/j.ijpharm.2016.09.048⟩. ⟨hal-01381133⟩