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Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery

Title
Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery
Authors
Lee H.Lytton-Jean A.K.R.Chen Y.Love K.T.Park A.I.Karagiannis E.D.Sehgal A.Querbes W.Zurenko C.S.Jayaraman M.Peng C.G.Charisse K.Borodovsky A.Manoharan M.Donahoe J.S.Truelove J.Nahrendorf M.Langer R.Anderson D.G.
Ewha Authors
이혁진
SCOPUS Author ID
이혁진scopus
Issue Date
2012
Journal Title
Nature Nanotechnology
ISSN
1748-3387JCR Link
Citation
vol. 7, no. 6, pp. 389 - 393
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Nanoparticles are used for delivering therapeutics into cells. However, size, shape, surface chemistry and the presentation of targeting ligands on the surface of nanoparticles can affect circulation half-life and biodistribution, cell-specific internalization, excretion, toxicity and efficacy. A variety of materials have been explored for delivering small interfering RNAs (siRNAs)ĝa therapeutic agent that suppresses the expression of targeted genes. However, conventional delivery nanoparticles such as liposomes and polymeric systems are heterogeneous in size, composition and surface chemistry, and this can lead to suboptimal performance, a lack of tissue specificity and potential toxicity. Here, we show that self-assembled DNA tetrahedral nanoparticles with a well-defined size can deliver siRNAs into cells and silence target genes in tumours. Monodisperse nanoparticles are prepared through the self-assembly of complementary DNA strands. Because the DNA strands are easily programmable, the size of the nanoparticles and the spatial orientation and density of cancer-targeting ligands (such as peptides and folate) on the nanoparticle surface can be controlled precisely. We show that at least three folate molecules per nanoparticle are required for optimal delivery of the siRNAs into cells and, gene silencing occurs only when the ligands are in the appropriate spatial orientation. In vivo, these nanoparticles showed a longer blood circulation time (t 1/2 24.2 min) than the parent siRNA (t 1/2 6 min).© 2012 Macmillan Publishers Limited.
DOI
10.1038/nnano.2012.73
Appears in Collections:
약학대학 > 약학과 > Journal papers
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