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

小干扰RNA 体内分布 核酸 生物物理学 体内 纳米技术 化学 内化 纳米颗粒 基因沉默 分散性 药物输送 转染 细胞 材料科学 体外 生物化学 生物 基因 生物技术 有机化学
作者
Hyukjin Lee,Abigail K. R. Lytton‐Jean,Yi Chen,Kevin T. Love,Angela I. Park,Emmanouil D. Karagiannis,Alfica Sehgal,William Querbes,Christopher Zurenko,Muthusamy Jayaraman,Chang G. Peng,Klaus Charissé,Anna Borodovsky,Muthiah Manoharan,Jessica Donahoe,Jessica Truelove,Matthias Nahrendorf,Róbert Langer,Daniel G. Anderson
出处
期刊:Nature Nanotechnology [Nature Portfolio]
卷期号:7 (6): 389-393 被引量:1115
标识
DOI:10.1038/nnano.2012.73
摘要

Nanoparticles are used for delivering therapeutics into cells1,2. 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 efficacy3,4,5,6,7. A variety of materials have been explored for delivering small interfering RNAs (siRNAs)—a therapeutic agent that suppresses the expression of targeted genes8,9. 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 toxicity10,11,12. 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 (t1/2 ≈ 24.2 min) than the parent siRNA (t1/2 ≈ 6 min). DNA strands can self-assemble into tetrahedral nanoparticles that can deliver small interfering RNA molecules to cells and suppress genes in tumours.
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