Remote-controlled release of DNA in living cells via simultaneous light and host-guest mediations.
Remote-controlled release of DNA in living cells via simultaneous light and host-guest mediations.
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DOI：
10.1021/ac502280z
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发表时间：
2014-10
影响因子：
7.4
通讯作者：
Jing Zheng;Yuhong Nie;Sheng Yang;Yue Xiao;Jishan Li;Yinhui Li;Ronghua Yang
中科院分区：
文献类型：
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作者：
Jing Zheng;Yuhong Nie;Sheng Yang;Yue Xiao;Jishan Li;Yinhui Li;Ronghua Yang
利用光子作为外部触发器实现寡核苷酸的远程控制释放，具有其他细胞内或外部刺激所无法比拟的上级优势。UV光由于效率高而成为有效的光子控制方式。然而，这些方法在活细胞中的进一步应用受到大剂量紫外光照射的阻碍。为了解决这个问题，本文提出了一个同时光和主/客调解。以巯基-β-环糊精（βCD）为载体，制备了金纳米粒子（AuNPs）。偶氮苯（Azo）标记在释放寡核苷酸上，充当光化学控制开关。二茂铁（Fe）是β-CD包合反应的优良客体，在紫外光照射下，它作为“增强剂”，改变了反式偶氮与β-CD包合-排阻过程的平衡，使紫外光照射剂量明显降低。为了进一步应用，转染的表达绿色荧光蛋白（GFP）的人肺癌A549细胞被用来确定细胞摄取和基因沉默介导的我们构建的系统在体内。结果表明，通过使用Fc宿主-客体相互作用，在30 min内实现了约62.4%的基因沉默，这显著高于没有Fc竞争的基因沉默。我们的策略提供了正交DNA递送和治疗活化的潜力，这将能够实现更高水平的位点特异性活性和减少的副作用。
Using photons as external triggers to realize remote-controlled release of oligonucleotide is superior to other intracellular or external stimulus. UV light is a valid photon-controlled manner due to high efficiency. However, further applications of these approaches in living cells are hampered by the large dose of UV-light irradiation. To address this issue, a simultaneous light and host/guest mediation was proposed in this paper. Gold nanoparticles (AuNPs) encoding with mercapto-β-cyclodextrin (βCD) served as a carried agent. Azobenzene (Azo), which was labeled on a releasing oligonucleotide, acted as a photochemically controlled switch. Ferrocene (Fc), an excellent guest for inclusion complexation by βCD, serves as "enhancers" and shifts the equilibrium of the inclusion-exclusion process between trans-Azo and βCD under UV-light irradiation, thus making the dose of UV-light irradiation reduced obviously. For further application, transfected green fluorescent protein (GFP)-expressing human lung cancer A549 cells were used to determine cellular uptake and gene silencing mediated by our constructed system in vivo. The results demonstrate that by employing Fc host-guest interaction, about 62.4% gene silencing was achieved within 30 min, which is significantly higher than that without Fc competition. Our strategy provides the potential for orthogonal DNA delivery and therapeutic activation that would be capable of achieving higher levels of site-specific activity and reduced amounts of side effects.