Membrane-spanning DNA nanopores with cytotoxic effect.
Membrane-spanning DNA nanopores with cytotoxic effect.
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DOI：
10.1002/anie.201405719
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发表时间：
2014-11-10
影响因子：
16.6
通讯作者：
Howorka, Stefan
中科院分区：
文献类型：
--
作者：
Burns, Jonathan R.;Al-Juffali, Noura;Janes, Sam M.;Howorka, Stefan
具有化学功能的自组装DNA纳米结构在纳米生物技术中引起了极大的兴趣。在本文中，化学修饰的DNA纳米孔被设计成刺穿细胞膜并引起细胞毒性。纳米孔由DNA寡核苷酸组装而成，在一端形成2 nm高的疏水带。该带由电荷中和的乙基硫代磷酸酯（EP）基团组成，其是降低细胞活力所需的。孔实现细胞杀伤的模式与共聚焦显微镜阐明。这项研究首次描述了DNA纳米孔与细胞的相互作用。该工作为未来开发具有癌症类型特异性的细胞毒性药物奠定了基础。化学在扩展DNA纳米结构的功能库中可以发挥重要作用。[1，2]设计的纳米材料已经通过为DNA支架[2，3]配备化学键来空间排列纳米颗粒，[4]荧光团[5]或蛋白质而开发。[6]这些DNA纳米结构主要应用于无细胞应用，但不用于细胞生物学，即使后者领域受益于纳米材料，如典型的核酸纳米结构所示。
Self-assembled DNA nanostructures with chemistry-enabled functionality are of great interest in nanobiotechnology. Herein, chemically modified DNA nanopores are designed to puncture cellular membranes and cause cytotoxicity. The nanopores are assembled from DNA oligonucleotides to form a 2 nm-high hydrophobic belt at one terminus. The belt is composed of charge-neutralized ethyl phosphorothioate (EP) groups which are required to decrease cell viability. The mode by which the pores achieve cell killing is elucidated with confocal microscopy. This study is the first to describe the interaction of DNA nanopores with cells. The work lays the foundation for the future development of cytotoxic agents with cancer type-specificity.Chemistry can play an important role in expanding the functional repertoire of DNA nanostructures.[1, 2] Designed nanomaterials have been developed by equipping DNA scaffolds [2, 3] with chemical linkages to spatially arrange nanoparticles,[4] fluorophores,[5] or proteins.[6] These DNA nanostructures have been mostly applied for cell-free applications but not for cell biology even though the latter field benefits from nanomaterials as demonstrated with canonical nucleic
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