Gold nanoparticles coated with polysarcosine brushes to enhance their colloidal stability and circulation time in vivo

J Colloid Interface Sci. 2016 Dec 1:483:201-210. doi: 10.1016/j.jcis.2016.08.038. Epub 2016 Aug 18.

Abstract

Polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, has been used to stabilize gold nanoparticles (AuNPs) due to its excellent hydrophilicity and biocompatibility. Disulfide functionalized polysarcosines with different molecular weight were synthesized and used to cap AuNPs by traditional ligand exchange. The grafting of PS on AuNPs was evidenced by Fourier transform infrared (FTIR) spectroscopy and the alternation of surface zeta potential. The polysarcosine coated AuNPs (Au@PS) showed good stabilities in wide pH range and saline condition. They had strong resistance to ligand competition of dithiothreitol (DTT). They showed good stability in serum, with a molecular weight dependent interaction pattern with proteins. The Au@PS had very low cytotoxicity and cell uptake in vitro. Based on the results in vitro, polysarcosine with molecular weight of 5kD with the best ability to stabilize AuNPs was used for in vivo test. The Au@PS had a longer circulation time in blood after intravenous injection than that of Au@PEG, indicating a better stealth-like property of polysarcosine. The Au@PS did not cause obvious toxicity in vivo, suggesting potential applications in disease diagnosis and therapy.

Keywords: Hydrophilic polypeptide; Long circulation; Nanomaterials; Polysarcosine.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Colloids
  • Disulfides / chemistry
  • Dithiothreitol / chemistry
  • Gold / chemistry*
  • Gold / pharmacokinetics
  • Gold / pharmacology
  • Heart / anatomy & histology
  • Heart / drug effects
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Hydrogen-Ion Concentration
  • Hydrophobic and Hydrophilic Interactions
  • Injections, Intravenous
  • Kidney / anatomy & histology
  • Kidney / drug effects
  • Liver / anatomy & histology
  • Liver / drug effects
  • Lung / anatomy & histology
  • Lung / drug effects
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Molecular Weight
  • Peptides / chemistry*
  • Peptides / pharmacokinetics
  • Peptides / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sarcosine / analogs & derivatives*
  • Sarcosine / chemistry
  • Sarcosine / pharmacokinetics
  • Sarcosine / pharmacology
  • Spleen / anatomy & histology
  • Spleen / drug effects

Substances

  • Colloids
  • Disulfides
  • Peptides
  • polysarcosine
  • Gold
  • Dithiothreitol
  • Sarcosine