Silver nanoscale antisense drug delivery system for photoactivated gene silencing

Paige K. Brown, Ammar T. Qureshi, Alyson N. Moll, Daniel J. Hayes, W. Todd Monroe

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

The unique photophysical properties of noble metal nanoparticles contribute to their potential as photoactivated drug delivery vectors. Here we demonstrate the synthesis and characterization of 60-80 nm silver nanoparticles (SNPs) decorated with thiol-terminated photolabile DNA oligonucleotides. In vitro assays and fluorescent confocal microscopy of treated cell cultures show efficient UV-wavelength photoactivation of surface-tethered caged ISIS2302 antisense oligonucleotides possessing internal photocleavable linkers. As a demonstration of the advantages of these novel nanocarriers, we investigate properties including: enhanced stability to nucleases, increased hybridization activity upon photorelease, and efficient cellular uptake as compared to commercial transfection vectors. Their potential as multicomponent delivery agents for oligonucleotide therapeutics is shown through regulation of ICAM-1 (Intracellular Adhesion Molecule-1) silencing. Our results suggest a means to achieve light-triggered, spatiotemporally controlled gene silencing via nontoxic silver nanocarriers, which hold promise as tailorable platforms for nanomedicine, gene expression studies, and genetic therapies.

Original languageEnglish (US)
Pages (from-to)2948-2959
Number of pages12
JournalACS nano
Volume7
Issue number4
DOIs
StatePublished - Apr 23 2013

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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