A New Hyaluronic Acid Derivative Obtained from Atom Transfer Radical Polymerization as a siRNA Vector for CD44 Receptor Tumor Targeting

Macromol Biosci. 2015 Nov;15(11):1605-15. doi: 10.1002/mabi.201500129. Epub 2015 Jul 1.

Abstract

Two derivatives of hyaluronic acid (HA) have been synthesized by atom transfer radical polymerization (ATRP), starting from an ethylenediamino HA derivative (HA-EDA) and by using diethylaminoethyl methacrylate (DEAEMA) as a monomer for polymerization. Both samples, indicated as HA-EDA-pDEAEMA a and b, are able to condense siRNA, as determined by gel retardation assay and resulting complexes show a size and a zeta potential value dependent on polymerization number, as determined by dynamic light scattering measurements. In vitro studies performed on HCT 116 cell line, that over express CD44 receptor, demonstrate a receptor mediated uptake of complexes, regardless of their surface charge.

Keywords: ATRP; CD44; hyaluronic acid; siRNA delivery; tumor targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Drug Delivery Systems / methods*
  • Genetic Vectors* / chemistry
  • Genetic Vectors* / pharmacology
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism*
  • Hyaluronic Acid* / chemical synthesis
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacology
  • Methacrylates / chemistry
  • Methacrylates / pharmacology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Neoplasms* / therapy
  • RNA, Small Interfering*

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • Methacrylates
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Hyaluronic Acid
  • diethylaminoethyl methacrylate