In situ tracking the intracellular delivery of antisense oligonucleotides by fluorescein doped silica nanoparticles

Antisense oligonucleotides (ASOs) are often utilized to interfere with gene expression at mRNA level for cancer treatment. Here, we synthesized fluorescein doped silica nanoparticles (FSNPs) and coated them by polyethyleneimine (PEI) for carrying ASOs. Agarose gel electrophoresis proved that PEI/FSNPs could load ASOs by a weight ratio as high as 30:1. We tracked the delivery process of ASOs from the ASOs/PEI/FSNPs composites to HeLa cells in situ by the confocal laser scanning microscopy (CLSM) techniques, including nuclear staining and Z-axis scanning. We found the ASOs/PEI/FSNPs composites exhibited their biological effects at specific intracellular localization, and the fluorescence of the FSNPs showed the dynamic delivery process in the cells.