Preparation, characterisation, and in vitro cancer-suppression function of RNA nanoparticles carrying miR-301b-3p Inhibitor

IF 3.8 4区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS IET nanobiotechnology Pub Date : 2023-03-09 DOI:10.1049/nbt2.12120

Junjie Zhao, Niu Niu, Fan Yang, Haitao Liu, Weibo Qi

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引用次数: 1

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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携带miR-301b-3p抑制剂的RNA纳米颗粒的制备、表征及其体外抑癌功能

多药耐药是肺腺癌(LUAD)化疗的最大障碍。对于部分顺铂(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)。方法NPs由miR-301b-3p、A549适配体(A549apt)和Cyanine 5以自下而上的方式组成，具有3路结(3WJ)结构。通过动态光散射、原生聚丙烯酰胺凝胶电泳和原子力显微镜观察纳米粒子的直径、组装过程和形态。采用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。结果3WJ-apt-miR分布均匀，直径为19.61±0.49 nm，呈三角形分支结构。A549适体具有特异性靶向性，保证了这种NP在体内的准确递送，其副作用比传统化疗小。这种纳米材料被癌细胞有效地内化，正常细胞活性完好无损。抑制了癌细胞的增殖、侵袭和迁移，增强了DDP敏感性，造成DNA损伤，促进DDP耐药细胞凋亡。结论基于RNA自组装，从基因调控角度研究了miRNA对LUAD患者DDP敏感性的影响。3WJ-apt-miR为临床肿瘤治疗铺平了道路。

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来源期刊

IET nanobiotechnology 工程技术-纳米科技

CiteScore

6.20

自引率

4.30%

发文量

审稿时长

1 months

期刊介绍： Electrical and electronic engineers have a long and illustrious history of contributing new theories and technologies to the biomedical sciences. This includes the cable theory for understanding the transmission of electrical signals in nerve axons and muscle fibres; dielectric techniques that advanced the understanding of cell membrane structures and membrane ion channels; electron and atomic force microscopy for investigating cells at the molecular level. Other engineering disciplines, along with contributions from the biological, chemical, materials and physical sciences, continue to provide groundbreaking contributions to this subject at the molecular and submolecular level. Our subject now extends from single molecule measurements using scanning probe techniques, through to interactions between cells and microstructures, micro- and nano-fluidics, and aspects of lab-on-chip technologies. The primary aim of IET Nanobiotechnology is to provide a vital resource for academic and industrial researchers operating in this exciting cross-disciplinary activity. We can only achieve this by publishing cutting edge research papers and expert review articles from the international engineering and scientific community. To attract such contributions we will exercise a commitment to our authors by ensuring that their manuscripts receive rapid constructive peer opinions and feedback across interdisciplinary boundaries. IET Nanobiotechnology covers all aspects of research and emerging technologies including, but not limited to: Fundamental theories and concepts applied to biomedical-related devices and methods at the micro- and nano-scale (including methods that employ electrokinetic, electrohydrodynamic, and optical trapping techniques) Micromachining and microfabrication tools and techniques applied to the top-down approach to nanobiotechnology Nanomachining and nanofabrication tools and techniques directed towards biomedical and biotechnological applications (e.g. applications of atomic force microscopy, scanning probe microscopy and related tools) Colloid chemistry applied to nanobiotechnology (e.g. cosmetics, suntan lotions, bio-active nanoparticles) Biosynthesis (also known as green synthesis) of nanoparticles; to be considered for publication, research papers in this area must be directed principally towards biomedical research and especially if they encompass in vivo models or proofs of concept. We welcome papers that are application-orientated or offer new concepts of substantial biomedical importance Techniques for probing cell physiology, cell adhesion sites and cell-cell communication Molecular self-assembly, including concepts of supramolecular chemistry, molecular recognition, and DNA nanotechnology Societal issues such as health and the environment Special issues. Call for papers: Smart Nanobiosensors for Next-generation Biomedical Applications - https://digital-library.theiet.org/files/IET_NBT_CFP_SNNBA.pdf Selected extended papers from the International conference of the 19th Asian BioCeramic Symposium - https://digital-library.theiet.org/files/IET_NBT_CFP_ABS.pdf