Fabrication of dihydroxyflavone-conjugated hyaluronic acid nanogels for targeted antitumoral effect

Colloids Surf B Biointerfaces. 2018 Nov 1:171:690-697. doi: 10.1016/j.colsurfb.2018.08.003. Epub 2018 Aug 6.

Abstract

We prepared hyaluronic acid (HA)-based nanogels conjugated with dihydroxyflavone (DHF) and evaluated their cellular uptake and antitumoral efficiency. 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) was used as a conjugation agent for esterification between DHF and HA as well as crosslinking among HA. The conjugations were confirmed by nuclear magnetic resonance spectroscopy, UV/vis spectroscopy, and high-performance liquid chromatography. The size and Zeta-potential of the DHF/HA nanogels were reduced with an increase in the concentration of DMTMM due to the involvement of more HA molecules for the conjugation reactions. The DHF/HA nanogel with a smaller size was greatly taken up by two kinds of tumor cells (HeLa and HepG2), compared to NIH3T3. The cell viabilities were reduced to approximately 60% for HeLa and HepG2 cells after 48 h post treatment with DHF/HA nanogels.

Keywords: Dihydroxyflavone; Hyaluronic acid; Nanogel; Tumor therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Flavones / chemistry
  • Flavones / pharmacology*
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • Mice
  • Molecular Structure
  • Morpholines / chemistry
  • NIH 3T3 Cells
  • Nanogels
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology*
  • Polyethyleneimine / chemistry
  • Polyethyleneimine / pharmacology*
  • Surface Properties

Substances

  • 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride
  • 6,7-dihydroxyflavone
  • Antineoplastic Agents
  • Flavones
  • Morpholines
  • Nanogels
  • polyethylene glycol polyethyleneimine nanogel
  • Polyethylene Glycols
  • Polyethyleneimine
  • Hyaluronic Acid