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

Int J Pharm. 2016 Nov 20;513(1-2):438-452. doi: 10.1016/j.ijpharm.2016.09.048. Epub 2016 Sep 15.

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).

MeSH terms

  • Biological Transport
  • Blood Proteins / chemistry
  • Blood Proteins / metabolism
  • Carcinoma, Hepatocellular
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Dioxanes* / administration & dosage
  • Dioxanes* / chemistry
  • Dioxanes* / pharmacology
  • Humans
  • Hydroxybutyrates* / administration & dosage
  • Hydroxybutyrates* / chemistry
  • Hydroxybutyrates* / pharmacology
  • L-Lactate Dehydrogenase / metabolism
  • Liver Neoplasms
  • Macrophages / metabolism
  • Malates* / administration & dosage
  • Malates* / chemistry
  • Malates* / pharmacology
  • Nanoparticles* / administration & dosage
  • Nanoparticles* / chemistry
  • Polyesters* / administration & dosage
  • Polyesters* / chemistry
  • Polyesters* / pharmacology
  • Polymers* / administration & dosage
  • Polymers* / chemistry
  • Polymers* / pharmacology

Substances

  • Blood Proteins
  • Cytokines
  • Dioxanes
  • Hydroxybutyrates
  • Malates
  • Polyesters
  • Polymers
  • poly(malic acid)
  • poly-beta-hydroxybutyrate
  • polytrimethylene carbonate
  • L-Lactate Dehydrogenase