Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery
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Author(s)
Sehgal, Alfica
Querbes, William
Zurenko, Christopher S.
Jayaraman, Muthusamy
Peng, Chang G.
Charisse, Klaus
Borodovsky, Anna
Manoharan, Muthiah
Donahoe, Jessica S.
Truelove, Jessica
Date Issued
June 2012
Journal
Nature Nanotechnology
Publisher
Nature Publishing Group
Citation
Lee, Hyukjin et al. “Molecularly Self-Assembled Nucleic Acid Nanoparticles for Targeted in Vivo siRNA Delivery.” Nature Nanotechnology 7.6 (2012): 389–393.
Version
Author's final manuscript
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)—a 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[subscript 1/2] ≈ 24.2 min) than the parent siRNA (t[subscript 1/2] ≈ 6 min).
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nnano.2012.73
