Bio-responsive alginate-keratin composite nanogels with enhanced drug loading efficiency for cancer therapy

Carbohydr Polym. 2017 Nov 1:175:159-169. doi: 10.1016/j.carbpol.2017.07.078. Epub 2017 Jul 29.

Abstract

This article presents a novel dual-stimuli responsive nanogel prepared from human hair keratin and alginate through simple crosslinking method. Keratin offer the crosslinking structure and bio-responsive ability and alginate ameliorated properties of nanogels including particle size, stability and drug loading capacity. The resultant keratin-alginate nanogels (KSA-NGs) could function as promising vectors for doxorubicin hydrochloride (DOX) with a super-high drug-loading rate of 52.9% (w/w) and dual-stimuli responsive behavior to GSH and trypsin. Cellular uptake results indicated DOX loaded KSA-NGs (DOX@KSA-NGs) are efficiently internalized in 4T1 and B16 cells in vitro, with a fast DOX release into cells under intracellular GSH and trypsin levels. In vitro cytotoxicity results further manifested that DOX@KSA-NGs behaved equivalent inhibition effects on tumor cells to DOX. In vivo experiments showed that DOX@KSA-NGs had a better anti-tumor effect and lower side effects compared to free drugs. These bio-responsive KSA-NGs have potential applications as nanocarriers for cancer therapy.

Keywords: Alginate; Doxorubicin; Enzyme-sensitive; GSH-sensitive; Human hair keratin; Nanogels.

MeSH terms

  • Alginates / chemistry*
  • Antibiotics, Antineoplastic / administration & dosage*
  • Cell Line, Tumor
  • Cell Survival
  • Doxorubicin / administration & dosage
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Gels
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Humans
  • Keratins / chemistry*
  • Nanostructures

Substances

  • Alginates
  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Gels
  • Hexuronic Acids
  • Keratins
  • Doxorubicin
  • Glucuronic Acid