Study of serum interaction with a cationic nanoparticle: Implications for in vitro endocytosis, cytotoxicity and genotoxicity

Int J Pharm. 2012 Feb 14;423(1):37-44. doi: 10.1016/j.ijpharm.2011.07.014. Epub 2011 Jul 27.

Abstract

We used well-characterized and positively charged nanoparticles (NP(+)) to investigate the importance of cell culture conditions, specifically the presence of serum and proteins, on NP(+) physicochemical characteristics, and the consequences for their endocytosis and genotoxicity in bronchial epithelial cells (16HBE14o-). NP(+) surface charge was significantly reduced, proportionally to NP(+)/serum and NP(+)/BSA ratios, while NP(+) size was not modified. Microscopy studies showed high endocytosis of NP(+) in 16HBE14o-, and serum/proteins impaired this internalization in a dose-dependent manner. Toxicity studies showed no cytotoxicity, even for very high doses of NP(+). No genotoxicity was observed with classic comet assay while primary oxidative DNA damage was observed when using the lesion-specific repair enzyme, formamidopyrimidine DNA-glycosylase (FPG). The micronucleus test showed NP(+) genotoxicity only for very high doses that cannot be attained in vivo. The low toxicity of these NP(+) might be explained by their high exocytosis from 16HBE14o- cells. Our results confirm the importance of serum and proteins on nanoparticles endocytosis and genotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Proteins / metabolism
  • Blood Proteins / pharmacology*
  • Cations / chemistry*
  • Cell Line
  • Cell Survival / drug effects*
  • Comet Assay
  • DNA Damage / drug effects*
  • DNA-Formamidopyrimidine Glycosylase / metabolism
  • Endocytosis / drug effects*
  • Endocytosis / physiology
  • Epichlorohydrin / chemistry
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology
  • Epoxy Compounds / chemistry
  • Humans
  • Micronucleus Tests
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity*
  • Particle Size
  • Polysaccharides / chemistry
  • Quaternary Ammonium Compounds / chemistry
  • Serum Albumin, Bovine / metabolism
  • Serum Albumin, Bovine / pharmacology
  • Static Electricity

Substances

  • Blood Proteins
  • Cations
  • Epoxy Compounds
  • Polysaccharides
  • Quaternary Ammonium Compounds
  • Epichlorohydrin
  • Serum Albumin, Bovine
  • glycidyl trimethylammonium
  • maltodextrin
  • DNA-Formamidopyrimidine Glycosylase