Department of Cardiothoracic Surgery, Affiliated Hospital of Jiaxing University (the First Hospital of Jiaxing), Jiaxing, Zhejiang, China.
IET Nanobiotechnol. 2023 May;17(3):224-233. doi: 10.1049/nbt2.12120. Epub 2023 Mar 9.
Multidrug resistance is the biggest barrier on the way to chemotherapy for lung adenocarcinoma (LUAD). For some LUAD patients with cisplatin (DDP) resistance and poor prognoses, the authors put forward RNA nanoparticles (NPs) carrying miR-301b-3p Inhibitor.
The NPs were composed of miR-301b-3p, A549 aptamer (A549apt), and Cyanine 5 in a bottom-up manner with a 3-way-junction (3WJ) structure. Diameter, assembly process, and morphology of NPs were observed by Dynamic Light Scattering, Native-Polyacrylamide Gel Electrophoresis, and Atomic Force Microscopy. Cell internalisation, toxicity, proliferation, migration, invasion, and apoptosis were assayed by confocal laser scanning microscope, CCK8, colony formation assay, Transwell, western blot, and flow cytometry.
3WJ-apt-miR was evenly distributed, with diameter of 19.61 ± 0.49 nm and triangular branching structures. The accurate delivery of this NP in vivo was ensured by A549 aptamer featuring specific targeting, with smaller side effects than traditional chemotherapy. Such nanomaterials were effectively internalized by cancer cells, with normal cell activity intact. Cancer cell proliferation, invasion, and migration were suppressed, and DDP sensitivity was enhanced, causing DNA damage and facilitating apoptosis of DDP-resistant cells.
Based on RNA self-assembling, the authors researched the effect of miRNA on DDP sensitivity in LUAD regarding gene regulation. 3WJ-apt-miR paves the way for clinical tumour therapy.
多药耐药性是肺腺癌 (LUAD) 化疗的最大障碍。对于一些顺铂 (DDP) 耐药且预后不良的 LUAD 患者，作者提出了携带 miR-301b-3p 抑制剂的 RNA 纳米颗粒 (NPs)。
NPs 采用自上而下的方法，由 miR-301b-3p、A549 适体 (A549apt) 和 Cy5 组成，具有 3 向结 (3WJ) 结构。通过动态光散射、天然聚丙烯酰胺凝胶电泳和原子力显微镜观察 NPs 的直径、组装过程和形态。通过共聚焦激光扫描显微镜、CCK8、集落形成实验、Transwell、western blot 和流式细胞术检测细胞内化、毒性、增殖、迁移、侵袭和凋亡。
3WJ-apt-miR 均匀分布，直径为 19.61 ± 0.49nm，具有三角形分支结构。A549 适体具有特异性靶向作用，确保了这种 NP 的体内精确传递，副作用小于传统化疗。这种纳米材料被癌细胞有效内化，正常细胞活性完好无损。癌细胞增殖、侵袭和迁移受到抑制，DDP 敏感性增强，导致 DNA 损伤，促进 DDP 耐药细胞凋亡。
基于 RNA 自组装，作者研究了 miRNA 对 LUAD 中基因调控下 DDP 敏感性的影响。3WJ-apt-miR 为临床肿瘤治疗铺平了道路。
