Design of multifunctional gold nanoparticles for in vitro and in vivo gene silencing

ACS Nano. 2012 Sep 25;6(9):8316-24. doi: 10.1021/nn3030223. Epub 2012 Aug 22.

Abstract

Over the past decade, the capability of double-stranded RNAs to interfere with gene expression has driven new therapeutic approaches. Since small interfering RNA (siRNAs, 21 base pair double-stranded RNA) was shown to be able to elicit RNA interference (RNAi), efforts were directed toward the development of efficient delivery systems to preserve siRNA bioactivity throughout the delivery route, from the administration site to the target cell. Here we provide evidence of RNAi triggering, specifically silencing c-myc protooncogene, via the synthesis of a library of novel multifunctional gold nanoparticles (AuNPs). The efficiency of the AuNPs is demonstrated using a hierarchical approach including three biological systems of increasing complexity: in vitro cultured human cells, in vivo invertebrate (freshwater polyp, Hydra ), and in vivo vertebrate (mouse) models. Our synthetic methodology involved fine-tuning of multiple structural and functional moieties. Selection of the most active functionalities was assisted step-by-step through functional testing that adopted this hierarchical strategy. Merging these chemical and biological approaches led to a safe, nonpathogenic, self-tracking, and universally valid nanocarrier that could be exploited for therapeutic RNAi.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallization / methods*
  • Gene Silencing*
  • Gold / chemistry*
  • Humans
  • Materials Testing
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure*
  • Particle Size
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics*
  • Transfection / methods*

Substances

  • Nanocapsules
  • RNA, Small Interfering
  • Gold