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

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.