Biological & Life Sciences, School of Arts & Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, Gujarat, 380009, India.
Sci Rep. 2022 Mar 18;12(1):4713. doi: 10.1038/s41598-022-08185-1.
MicroRNAs (miRNAs) are single-stranded, non-coding, 19-25 nucleotide RNA molecules that have been observed to be dysregulated in many diseases including cancer. miRNAs have been known to play an important role in cellular proliferation, differentiation, migration, apoptosis, survival, and morphogenesis. Breast cancer is heterogeneous in nature and contributed extensively to the increased mortality rate. miRNA can either be tumor-suppressive or oncogenic in nature. The level of expression of miRNA changes according to the subtypes of cancer and the mutation responsible for different cancers. miRNA mimicry or inhibition are emerging possible therapies to maintain the level of miRNA inside the cells. In order to have proper miRNA mimicry, the major hurdle is to deliver the miRNA mimics at the site of tumor. Metallic nanoparticles with modified surface can be used to solve the problem of miRNA delivery. MiR-206 is reported to be down-regulated in Luminal-A type of breast cancer. In the current manuscript, we aim to modify the surface of gold-nanoparticles (AuNPs) with PEG moiety and allow miRNA to attach to it. The fabricated nano-complex, not only delivered miR-206 but also caused cell death in MCF-7 by arresting cells in the G0-G1 phase and inducing apoptosis by downregulating NOTCH 3.
微小 RNA(miRNA)是单链、非编码、19-25 个核苷酸的 RNA 分子,在许多疾病中都观察到其失调,包括癌症。miRNA 在细胞增殖、分化、迁移、凋亡、存活和形态发生中起着重要作用。乳腺癌本质上是异质的,并在很大程度上导致死亡率增加。miRNA 本质上可以是肿瘤抑制物或致癌的。miRNA 的表达水平根据癌症的亚型和导致不同癌症的突变而变化。miRNA 模拟或抑制是新兴的可能治疗方法,可以维持细胞内 miRNA 的水平。为了进行适当的 miRNA 模拟,主要的障碍是将 miRNA 模拟物递送到肿瘤部位。经过修饰表面的金属纳米颗粒可用于解决 miRNA 递送的问题。据报道,miR-206 在 Luminal-A 型乳腺癌中下调。在本手稿中,我们旨在用 PEG 部分修饰金纳米颗粒(AuNPs)的表面,并允许 miRNA 附着在其上。所制备的纳米复合物不仅递送了 miR-206,还通过下调 NOTCH3 使 MCF-7 细胞停滞在 G0-G1 期并诱导细胞凋亡,从而导致细胞死亡。