This study demonstrated a chemotherapy drug-free delivery system for breast cancer treatment based on a simple DNA nanostructure composed of sequence 1 containing ATP and AS1411 aptamers and sequence 2 containing antimiR-21. The DNA nanostructure was used for co-delivery of KLA peptide and antimiR-21 as antiapoptotic agents. These therapeutic agents could not be internalised into eukaryotic cells freely which is one of the great features of this targeting platform. The presented delivery system was ATP-responsive, leading to disassembly of the DNA nanostructure in high ATP concentration of cancer cells and restoration of the function of antimiR-21 in these cells. The DNA nanostructure was associated with high cellular uptake by MCF-7 and 4T1 cells due to expression of nucleolin as target of AS1411 on their plasma membranes, while the developed targeting platform could not be internalised into CHO cells because of lack of the active targeting moiety on their surfaces. Furthermore, the results showed that co-delivery of antimiR-21 and KLA peptide using the DNA nanostructure could efficiently prohibit tumour growth in vitro and in vivo and induce a synergistic anticancer activity. Thus, this work provides a new ATP-responsive nanotargeting delivery system and synergistic chemotherapy drug-free regimen for cancer treatment.

该研究展示了一种用于乳腺癌治疗的无化疗药物递送系统，该系统基于简单的 DNA 纳米结构，该结构由包含 ATP 和 AS1411 适体的序列 1 和包含 antimiR-21 的序列 2 组成。DNA 纳米结构用于共同递送 KLA 肽和 antimiR-21 作为抗细胞凋亡剂。这些治疗剂不能自由地内化到真核细胞中，这是该靶向平台的一大特点。所提出的传递系统是 ATP 响应的，导致 DNA 纳米结构在高 ATP 浓度的癌细胞中分解，并恢复这些细胞中 antimiR-21 的功能。DNA 纳米结构与 MCF-7 和 4T1 细胞的高细胞摄取相关，因为核仁蛋白在其质膜上作为 AS1411 的靶标表达，而开发的靶向平台由于其表面缺乏活性靶向部分而无法内化到 CHO 细胞中。此外，结果表明，使用 DNA 纳米结构共同递送 antimiR-21 和 KLA 肽可以有效地抑制肿瘤生长在体外和体内并诱导协同抗癌活性。因此，这项工作为癌症治疗提供了一种新的 ATP 响应纳米靶向递送系统和协同化疗无药方案。