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.


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
  • Prohibitins


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