Delivery of Quantum Dot-siRNA Nanoplexes in SK-N-SH Cells for BACE1 Gene Silencing and Intracellular Imaging

作者：Li, Shengliang; Liu, Zhonghua; Ji, Fengtao; Xiao, Zijian; Wang, Minjuan; Peng, Yingji; Zhang, Yulin; Liu, Ling; Liang, Zibing; Li, Feng^*

来源：Molecular Therapy - Nucleic Acids, 2012, 1(4): e20.

DOI：10.1038/mtna.2012.11

• Alzheimer's disease
• BACE1
• quantum dot
• siRNA
• SK-N-SH cells

The fluorescent quantum dots (QDs) delivered small interfering RNAs (siRNAs) targeting beta-secretase (BACE1) to achieve high transfection efficiency of siRNAs and reduction of beta-amyloid (A beta) in nerve cells. The CdSe/ZnS QDs with the conjugation of amino-polyethylene glycol (PEG) were synthesized. Negatively charged siRNAs were electrostatically adsorbed to the surface of QDs to develop QD-PEG/siRNA nanoplexes. The QD- PEG/siRNAs nanoplexes significantly promote the transfection efficiency of siRNA, and the siRNAs from non- packaged nanoplexes were widely distributed in cell bodies and processes and efficiently silenced BACE1 gene, leading to the reduction of A beta. The biodegradable PEG polymer coating could protect QDs from being exposed to the intracellular environment and restrained the release of toxic Cd2 . Therefore, the QD-PEG/siRNA nanoplexes reported here might serve as ideal carriers for siRNAs. We developed a novel method of siRNA delivery into nerve cells. We first reported that the QD-PEG/siRNA nanoplexes were generated by the electrostatic interaction and inhibited the Alzheimer's disease (AD)-associated BACE1 gene. We also first revealed the dynamics of QD-PEG/siRNAs within nerve cells via confocal microscopy and the ultrastructural evidences under transmission electron microscopy (TEM). This technology might hold promise for the treatment of neurodegenerative diseases such as AD.

• 出版日期2012-4
• 单位中山大学