Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment. To accomplish this, we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation. This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer, AS1411, and a replaceable anti-biomarker probe (ABP). We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS1411 and then activated by the presence of a given intracellular biomarker. By using such a belt-and-braces strategy, this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells. Moreover, since the expression level of biomarkers tends to indicate the specific physiological state of individual cells, biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.

中文翻译：

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在细胞水平上设计定制的纳米药物递送系统，用于靶向癌症治疗。

为单个细胞定制的药物管理可以从本质上解决癌症的异质性，并为提供个性化治疗提供安全有效的方法。为了实现这一目标，我们开发了一种智能纳米药物输送系统，其特征在于靶向癌细胞的药物输送和细胞内生物标记物响应药物的激活。该系统由一个长刻痕的DNA双链体组成，该双链体是通过两个延伸的反义寡核苷酸串联杂交而形成的，它们的末端分别被癌细胞特异性适体AS1411和可替换的抗生物标记探针（ABP）封闭。我们证明了这种DNA纳米药物在AS1411的指导下直接作用于癌细胞，然后被给定的细胞内生物标记物激活。通过使用这样的“一刀切”策略，这种DNA纳米药物系统可以安全有效地加速靶癌细胞的凋亡。此外，由于生物标志物的表达水平趋向于指示单个细胞的特定生理状态，因此预期纳米药物的生物标志物响应性激活将能够在细胞水平上进行定制的药物施用。