Chemically Modified Dendritic Starch: A Novel Nanomaterial for siRNA Delivery

Bioconjug Chem. 2015 Aug 19;26(8):1766-74. doi: 10.1021/acs.bioconjchem.5b00313. Epub 2015 Aug 11.

Abstract

Nanostructured starches are naturally derived nanomaterials that can be chemically modified to allow for the introduction of functional groups, enhancing their potential for drug delivery and other biotechnology applications. In this proof of concept study, we investigate chemically modified, enzymatically synthesized glycogen (ESG) nanodendrites as a biodegradable, biocompatible, siRNA delivery system. Commercially available ESG was modified using glycidyltrimethylammonium chloride (GTMA), introducing quaternary ammonium groups via an epoxide ring opening reaction. This cationic ESG (cESG) electrostatically bound siRNA and successfully knocked down protein expression in an in vitro ovarian clear cell carcinoma model. The construct exhibited sustained siRNA delivery for up to 6 days while exhibiting less toxicity than a common liposome-based siRNA delivery reagent, Lipofectamine RNAiMAX. These promising results set the stage for the use of dendritic starch as a cost-effective, easily modifiable nanoscale delivery system for a diverse range of cargo including nucleic acids and therapeutic compounds.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cations
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Epoxy Compounds / chemistry
  • Female
  • Glycogen / chemistry*
  • Humans
  • Liposomes
  • Magnetic Resonance Spectroscopy
  • Microscopy, Electron, Transmission
  • Nanostructures / chemistry*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / genetics
  • Photoelectron Spectroscopy
  • Quaternary Ammonium Compounds / chemistry
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • Spectroscopy, Fourier Transform Infrared
  • Starch / chemistry*
  • Superoxide Dismutase / antagonists & inhibitors*
  • Superoxide Dismutase / genetics
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Cations
  • Drug Carriers
  • Epoxy Compounds
  • Liposomes
  • Quaternary Ammonium Compounds
  • RNA, Small Interfering
  • glycidyl trimethylammonium
  • Starch
  • Glycogen
  • Superoxide Dismutase
  • superoxide dismutase 2