A DNA-Device that Mediates Selective Endosomal Escape and Intracellular Delivery of Drugs and Biologicals.
A DNA-Device that Mediates Selective Endosomal Escape and Intracellular Delivery of Drugs and Biologicals.
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一种介导选择性内体逃逸以及药物和生物制品的细胞内递送的 DNA 装置。
DOI：
10.1002/adfm.201303188
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发表时间：
2014-05-21
影响因子：
19
通讯作者：
Muro, Silvia
中科院分区：
文献类型：
--
作者：
Muro, Silvia
设计用于辅助药物细胞内递送的材料可极大地改善医疗治疗。虽然DNA是一种难以引入细胞的分子，但DNA可被设计成能够进行细胞内递送的装置。然而，由不含其他结构材料、尺寸大于非特异性穿透相关尺寸且靶向能力足以克服非特异性途径的DNA装置介导的运输尚未实现。这项研究表明这是可能的。由DNA构建的亚微米（200纳米）树枝状大分子（核树枝状大分子（NDs））与针对选定细胞表面受体的抗体偶联，并与聚合物纳米颗粒（NPs）进行比较。NDs和NPs特异性结合表达这些靶点的细胞，并通过与选定受体相关的途径有效地进入细胞。虽然NPs运输到核周内溶酶体，但NDs仍分散在整个细胞中，这表明其从内体逃逸。这在体外得到了证实，在体外，NDs在内体样pH下破坏膜性囊泡，并且在细胞培养中，它们：使模型药物、糖类、蛋白质和核酸从内体逃逸；允许进入其他细胞内区室；导致货物产生可测量的效果；且不引起细胞毒性。因此，这些DNA纳米装置可用于选择性地克服细胞内屏障，突显了DNA材料日益广泛的应用范围。
Design of materials to aid intracellular delivery of agents can greatly improve medical treatments. While DNA is a molecule difficult to introduce into cells, DNA can be engineered into devices capable of intracellular delivery. Yet, transport mediated by DNA-devices void of other structural material, with size greater than that associated with non-specific penetration, and with targeting capacity enough to overcome non-specific pathways has not been achived. This study demonstrates that this is possible. Submicrometer (200-nm) dendrimers built of DNA (nucleodendrimers (NDs)) are coupled to antibodies against selected cell-surface receptors and compared to polymer nanoparticles (NPs). NDs and NPs bind specifically to cells expressing these targets and efficiently enter cells via the pathway associated with the selected receptor. While NPs traffic to perinuclear endo-lysosomes, NDs remain scattered throughout the cell, suggesting endosomal escape. This is confirmed in vitro, where NDs disrupt membranous vesicles at endosomal-like pH and in cell culture, where they: provide endosomal escape of model drugs, sugars, proteins, and nucleic acids; allow access to other intracellular compartments; result in measurable effects of cargoes; and do not cause cytotoxicity. Therefore, these DNA-nanodevices can be used to selectively overcome intracellular barriers, underscoring the growing range of applications of DNA materials.
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表面纳米技术与内吞作用之间的新兴联系：对非病毒基因递送的影响。
影响因子：
17.4
作者：
Adler AF;Leong KW
通讯作者：
Leong KW
影响因子：
4.9
作者：
Kim, Kyoung-Ran;Kim, Da-Rae;Ahn, Dae-Ro
通讯作者：
Ahn, Dae-Ro
DOI：
10.1016/j.jconrel.2010.10.031
发表时间：
2011-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Hsu J;Serrano D;Bhowmick T;Kumar K;Shen Y;Kuo YC;Garnacho C;Muro S
通讯作者：
Muro S
影响因子：
64.8
作者：
JEFFERIES, WA;BRANDON, MR;MASON, DY
通讯作者：
MASON, DY
DOI：
10.1039/c2cc37471d
发表时间：
2012-12-25
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Keum JW;Bermudez H
通讯作者：
Bermudez H