Nanobiotech Lab, Department of Zoology, Kirori Mal College, University of Delhi, Delhi, 110007, India.
NBRC, Department of Biological Sciences, Alabama State University, AL 36104, USA.
Nanomedicine (Lond). 2024 Apr;19(10):895-914. doi: 10.2217/nnm-2023-0325. Epub 2024 Mar 26.
Osteoporosis is a systemic skeletal disorder characterized by reduced osteoblast differentiation, predominantly by overexpression of the gene. A layer-by-layer approach enabled encapsulation of siRNA to enhance the short half-life and poor transfection capacity of siRNA. Polyethyleneimine and siRNA on chitosan-coated gold nanoparticles (PEI/siRNA/Cs-AuNPs) were engineered using chitosan-reduced gold nanoparticles. They were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared and gel-mobility assays. Detailed experiments, gene silencing and western blots were performed. A total of 80% knockdown of the target sclerostin protein was observed by PEI/siRNA/Cs-AuNPs, q-PCR showed threefold downregulation of the gene. Osteogenic markers and were significantly upregulated. We report a safe, biocompatible nanotherapeutic strategy to enhance siRNA protection and subsequent silencing to augment bone formation.
骨质疏松症是一种全身性骨骼疾病,其特征是成骨细胞分化减少,主要表现为 基因过表达。通过层层包裹的方法将 siRNA 封装起来,可以增强 siRNA 的半衰期短和转染效率差的缺点。聚乙烯亚胺和壳聚糖包覆的金纳米粒子上的 siRNA(PEI/siRNA/Cs-AuNPs)是利用壳聚糖还原金纳米粒子而构建的。采用动态光散射、扫描电子显微镜、透射电子显微镜、傅里叶变换红外光谱和凝胶迁移分析对其进行了表征。并进行了详细的实验、基因沉默和 Western blot 实验。PEI/siRNA/Cs-AuNPs 可使靶基因骨硬化蛋白的表达量降低 80%,q-PCR 结果显示 基因的表达水平下调了 3 倍。成骨标志物 和 显著上调。我们报告了一种安全、生物相容的纳米治疗策略,以增强 siRNA 的保护作用,进而增强骨形成。