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

João Conde, Alfredo Ambrosone, Vanesa Sanz, Yulan Hernandez, Valentina Marchesano, Furong Tian, Hannah Child, Catherine C. Berry, M. Ricardo Ibarra, Pedro V. Baptista, Claudia Tortiglione, Jesus M. De La Fuente

Research output: Contribution to journalArticlepeer-review

180 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8316-8324
Number of pages9
JournalACS Nano
Volume6
Issue number9
DOIs
Publication statusPublished - 25 Sep 2012

Keywords

  • animal models
  • biofunctionalization
  • c-myc
  • cancer
  • gold nanoparticles
  • RNA interference

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