title: Silver nanoscale antisense drug delivery system for photoactivated gene silencing.
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.
authors.affiliation: Biological and Agricultural Engineering, Louisiana State University and LSU AgCenter, Baton Rouge, Louisiana 70803, United States.
authors.forename: Paige K
authors.initials: PK
authors.lastname: Brown
authors.forename: Ammar T
authors.initials: AT
authors.lastname: Qureshi
authors.forename: Alyson N
authors.initials: AN
authors.lastname: Moll
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hayes
authors.forename: W Todd
authors.initials: WT
authors.lastname: Monroe
mesh_terms: D016373:DNA, Antisense / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000528:radiation effects / Q000648:ultrastructure*; D053769:Nanocapsules / Q000737:chemistry* / Q000528:radiation effects* / Q000648:ultrastructure; D010316:Particle Size; D012834:Silver / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: D016373:DNA, Antisense; D053769:Nanocapsules; D018799:Intercellular Adhesion Molecule-1; D012834:Silver