State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha, China.
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha, China.
Talanta. 2018 Jun 1;183:11-17. doi: 10.1016/j.talanta.2018.02.036. Epub 2018 Feb 10.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulated diverse cellular processes including differentiation, proliferation, apoptosis, metabolism and signal transduction pathways. An increasing number of data suggested that miRNA-21 could be identified as diagnostic and therapeutic biomarker for breast cancer. Meanwhile, inhibiting the function of miRNA-21, resulting in cells growth inhibition and apoptotic cells death. To realize miRNA-21detection and inhibition to diagnostic and therapeutic breast cancer cells, we developed gold nanoparticle-based 2'-O-methyl modified DNA probes (AuNP-2'-OMe-DNA probes) for diagnostic and therapeutic breast cancer. Gold nanoparticles were functionalized with chemically modified miRNA-21 inhibitor to suppress the function of miRNA-21 for the therapeutic breast cancer, at the same time, fluorophore-labeled DNA molecules were hybridized with antimiRNA-21 for diagnostic breast cancer. The results showed that the 2'-O-methyl modified DNA can improve stability, increase binding affinity to target strands and enhance the therapeutic effects. The experimental results also demonstrated that antimiR-21 were efficiently introduced into the cells and knocked down miRNA-21 to inhibit its function, leading to growth inhibition and apoptotic cells death. We prospected that chemically modified miRNA-21 inhibitor based on gold nanoparticles would be as a promising diagnostic and therapeutic platform for breast cancer clinically.
微小 RNA(miRNAs)是一类小的非编码 RNA,可以调节多种细胞过程,包括分化、增殖、凋亡、代谢和信号转导途径。越来越多的数据表明,miRNA-21 可以作为乳腺癌的诊断和治疗生物标志物。同时,抑制 miRNA-21 的功能会导致细胞生长抑制和凋亡细胞死亡。为了实现 miRNA-21 的检测和抑制,用于诊断和治疗乳腺癌细胞,我们开发了基于金纳米颗粒的 2'-O-甲基修饰 DNA 探针(AuNP-2'-OMe-DNA 探针)用于诊断和治疗乳腺癌。金纳米颗粒通过化学修饰的 miRNA-21 抑制剂进行功能化,以抑制 miRNA-21 的功能,用于治疗乳腺癌,同时,荧光标记的 DNA 分子与抗 miRNA-21 杂交,用于诊断乳腺癌。结果表明,2'-O-甲基修饰的 DNA 可以提高稳定性,增加与靶链的结合亲和力,并增强治疗效果。实验结果还表明,抗 miR-21 可以有效地被引入细胞,敲低 miRNA-21 以抑制其功能,导致细胞生长抑制和凋亡。我们预计,基于金纳米颗粒的化学修饰 miRNA-21 抑制剂将成为一种有前途的用于临床乳腺癌的诊断和治疗平台。