Exploring Electrically Controlled Delivery Systems for Nucleic Acid Therapeutics

Antisense oligonucleotides (ASOs) show therapeutic promise but face delivery challenges. This thesis explores iontronic micropipettes—electrophoretic devices with ion-exchange membranes—for localized ASO delivery. In vitro experiments targeting enhanced green fluorescent protein (eGFP) mRNA in human head and neck squamous cell carcinoma cells showed ineffective silencing with unmodified ASOs, while lipid-based transfection achieved partial knockdown, highlighting limitations in cellular uptake. Iontronic delivery confirmed ASO transport via UV absorbance, though success declined with extensively modified ASOs and altered membrane formulations. Delivery to 3D spheroids embedded in hydrogel showed no clear gene silencing, emphasizing the need for further optimization. These findings offer preliminary support for iontronic micropipettes as ASO delivery tools and identify key barriers to functional efficacy.