ACS Nano. 2019 Jan 22;13(1):706-717. doi: 10.1021/acsnano.8b07948. Epub 2018 Dec 19.
Displaying the advantage of nanoparticles in cancer targeting and drug delivery, micelles have shown great potential in cancer therapy. The mechanism for micelle targeting to cancer without the need for ligands is due to the size advantage of micelles within the lower end of the nanometer scale that is the optimal size for favoring the enhanced permeability and retention (EPR) effect while escaping trapping by macrophages. MicroRNAs are ubiquitous and play critical roles in regulating gene expression, cell growth, and cancer development. However, their in vivo delivery in medical applications is still challenging. Here, we report the targeted delivery of anti-miRNA to cancers via RNA micelles. The phi29 packaging RNA three-way junction (pRNA-3WJ) was used as a scaffold to construct micelles. An oligo with 8nt locked nucleic acid (LNA) complementary to the seed region of microRNA21(miR21) was included in the micelles as an interference molecule for cancer inhibition. These RNA micelles carrying anti-miR21 exhibited strong binding and internalization to cancer cells, inhibited the function of oncogenic miR21, enhanced the expression of the pro-apoptotic factor, and induced cell apoptosis. Animal trials revealed effective tumor targeting and inhibition in xenograft models. The inclusion of folate as a targeting ligand in the micelles did not show significant improvement of the therapeutic efficacy in vivo, suggesting that micelles can carry therapeutics to a target tumor and inhibit its growth without ligands.
展示了纳米颗粒在癌症靶向和药物输送方面的优势，胶束在癌症治疗中显示出巨大的潜力。胶束无需配体即可靶向癌症的机制是由于胶束的尺寸优势，其尺寸在纳米尺度的低端范围内，这是促进增强通透性和保留（EPR）效应的最佳尺寸，同时避免被巨噬细胞捕获。microRNAs 是普遍存在的，在调节基因表达、细胞生长和癌症发展中发挥着关键作用。然而，它们在医学应用中的体内输送仍然具有挑战性。在这里，我们通过 RNA 胶束报告了针对癌症的抗 miRNA 的靶向递药。phi29 包装 RNA 三链结（pRNA-3WJ）被用作构建胶束的支架。胶束中包含一条与 microRNA21（miR21）的种子区域互补的 8nt 锁核酸（LNA）寡核苷酸，作为抑制癌症的干扰分子。这些携带抗 miR21 的 RNA 胶束表现出对癌细胞的强烈结合和内化作用，抑制了致癌 miR21 的功能，增强了促凋亡因子的表达，并诱导细胞凋亡。动物试验显示在异种移植模型中具有有效的肿瘤靶向和抑制作用。将叶酸作为配体包含在胶束中并没有显著提高体内治疗效果，这表明胶束可以携带治疗剂到靶肿瘤并抑制其生长而无需配体。
