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

Abstract

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.

Keywords: HepaRG cells; Macrophages; Nanoparticle; Poly(hydroxy alkanoate); Poly(malic acid); Poly(trimethylene carbonate).