Injectable Polyplex Hydrogel for Localized and Long-Term Delivery of siRNA

ACS Nano. 2012 Jul 24;6(7):5757-66. doi: 10.1021/nn300842a. Epub 2012 Jun 8.

Abstract

Here, we describe a concept for localized and long-term delivery of short interfering RNA (siRNA) using an injectable polyplex hydrogel possessing thermosensitivity and biodegradability properties. We prepared a low molecular weight polyethyleneimine-poly(organophosphazene) conjugate as a thermosensitive and cationic polymer that has a cleavable ester linkage. The conjugates formed about 100 nm sized polyplexes with siRNAs, and the polyplex solution turned into a polyplex hydrogel at body temperature via a hydrophobic interaction. We injected the polyplex hydrogel with siRNA of cyclin B1, an essential protein for controlling the cell cycle, into the tumor xenograft model. Polyplexes were slowly released from the polyplex hydrogel by dissolution and degradation, allowing an in vivo antitumor effect via cyclin B1 gene silencing for 4 weeks with only a single injection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cyclin B1 / antagonists & inhibitors
  • Cyclin B1 / genetics
  • Delayed-Action Preparations
  • Drug Delivery Systems*
  • Gene Silencing
  • Humans
  • Hydrogels
  • Injections
  • Male
  • Mice
  • Mice, Nude
  • Molecular Weight
  • Nanoconjugates / chemistry
  • Nanotechnology
  • Organophosphorus Compounds / chemical synthesis
  • Organophosphorus Compounds / chemistry
  • Particle Size
  • Phase Transition
  • Polyethyleneimine / chemical synthesis
  • Polyethyleneimine / chemistry
  • Polymers / chemical synthesis
  • Polymers / chemistry
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • Viscosity
  • Xenograft Model Antitumor Assays

Substances

  • Cyclin B1
  • Delayed-Action Preparations
  • Hydrogels
  • Nanoconjugates
  • Organophosphorus Compounds
  • Polymers
  • RNA, Small Interfering
  • poly(organophosphazene)
  • Polyethyleneimine