Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery.
Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery.
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DOI：
10.1038/nnano.2012.73
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发表时间：
2012-06-03
影响因子：
38.3
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中科院分区：
文献类型：
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纳米颗粒用于将治疗递送到细胞中已经探索了用于传递小型干扰RNA（siRNA）的材料 - 一种抑制靶向基因表达的治疗剂诸如脂质体和聚合系统的纳米颗粒的大小，组成和表面化学是异质的，这可以导致次优性能，缺乏组织特异性和潜在的毒性，我们在这里表明，自组装的DNA DNA四面体纳米颗粒具有良好定义的尺寸。可以通过互补DNA链的自组装制备单分散纳米颗粒中的siRNA和肿瘤中的静音靶基因。由于DNA链很容易编程，因此纳米颗粒的大小以及靶向配体的癌症的空间取向和密度（例如，辣椒和叶酸）在纳米粒子表面上可以精确控制。最佳的siRNA递送到细胞中，仅当配体在适当的空间方向时才会发生基因沉默。循环时间（T1/2至24.2分钟）比父siRNA（T1/2至6分钟）。
Nanoparticles are employed 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, 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 precisely controlled. We show that at least three folate molecules per nanoparticle is 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).
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影响因子：
16.6
作者：
Bhatia, Dhiraj;Surana, Sunaina;Krishnan, Yamuna
通讯作者：
Krishnan, Yamuna
影响因子：
64.8
作者：
Soutschek, J;Akinc, A;Vornlocher, HP
通讯作者：
Vornlocher, HP
影响因子：
13.3
作者：
Keum, Jung-Won;Ahn, Jin-Ho;Bermudez, Harry
通讯作者：
Bermudez, Harry
影响因子：
46.9
作者：
通讯作者：
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影响因子：
38.3
作者：
通讯作者：
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