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Design of multifunctional gold nanoparticles for in vitro and in vivo gene silencing.
ACS Nano 6, 8316-8324 (2012)
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gold Nanoparticles ; Rna Interference ; Animal Models ; Biofunctionalization ; C-myc ; Cancer; INTERFERING RNA DELIVERY; SIRNA DELIVERY; QUANTUM DOTS; CELLS
ISSN (print) / ISBN 1936-0851
Zeitschrift ACS Nano
Quellenangaben Band: 6, Heft: 9, Seiten: 8316-8324
Verlag American Chemical Society (ACS)
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Biology (ILBD)