MicroRNAs play an important role in tumorigenesis and, among them, miR-21 is found to be aberrantly up-regulated in various tumors. The tumor-associated antigen, folate receptor alpha is a GPI-membrane protein overexpressed in many malignant tumors of epithelial origin, including ovarian and cervical cancers. Covalently bound octahedral DNA nanocages were functionalized with folate molecules and utilized as scaffolds to engineer four sequestering units with a miR-21 complementary sequence for obtaining biocompatible Fol-miR21-NC non-toxic nanostructures, to be able to selectively recognize folate receptor alpha-overexpressing cancer cells and sequester the oncogenic miR-21. qPCR assays showed that Fol-miR21-NCs reduce the miR-21 expression up to 80% in cancer cells in the first 2 days of treatment. Functional assays demonstrated that miR-21 sequestering leads to up-regulation of miR-21 tumor suppressor targets (i.e., PTEN and Pdcd4), reduction in cancer cell migration, reduction in proliferation, and increase in cell death. Fol-miR21-NCs can be efficiently loaded with the chemotherapeutic agent doxorubicin. Co-delivery of anti-miR-21 and doxorubicin showed additive cytotoxic effects on tumor cells, paving the way for their use as selective nucleic acid drugs.

MicroRNAs 在肿瘤发生中发挥重要作用，其中 miR-21 在各种肿瘤中异常上调。肿瘤相关抗原叶酸受体 α 是一种 GPI 膜蛋白，在许多上皮起源的恶性肿瘤中过度表达，包括卵巢癌和宫颈癌。共价结合的八面体 DNA 纳米笼用叶酸分子功能化并用作支架来设计四个具有 miR-21 互补序列的隔离单元，以获得生物相容性 Fol-miR21-NC 无毒纳米结构，从而能够选择性识别叶酸受体 α 过表达癌细胞并隔离致癌 miR-21。qPCR 分析表明，Fol-miR21-NCs 在治疗的前 2 天将癌细胞中 miR-21 的表达降低了 80%。功能分析表明，miR-21 隔离导致 miR-21 肿瘤抑制靶标（即 PTEN 和 Pdcd4）上调、癌细胞迁移减少、增殖减少和细胞死亡增加。Fol-miR21-NCs 可以有效地装载化学治疗剂阿霉素。抗 miR-21 和多柔比星的共同给药显示出对肿瘤细胞的附加细胞毒作用，为它们用作选择性核酸药物铺平了道路。