Synthetic Conjugated Oligoelectrolytes Are Effective siRNA Transfection Carriers: Relevance to Pancreatic Cancer Gene Therapy

Abstract

Conjugated oligoelectrolyte COE-S6 contains an elongated conjugated core with three cationic charges at each termini of the internal core. As an analogue of bolaamphiphiles, these structural attributes lead to the formation of spherical nanoplexes with D_h = 205 ± 5.0 nm upon mixing with small interfering RNA (siRNA). COE-S6/siRNA nanocomplexes were shown to be protective toward RNase, stimulate endosome escape, and achieve transfection efficiencies comparable to those achieved with commercially available LIP3000. Moreover, COE-S6/siRNA nanocomplexes enabled efficient silencing of the K-ras gene in pancreatic cancer cells and significant inhibition of cancer tumor growth with negligible in vitro toxicities. More importantly, cell invasion and colony formation of the Panc-1 cells were significantly inhibited, and apoptosis of the pancreatic cancer cells was also promoted. We also note that COE-S6 is much less toxic relative to commercial lipid formulations, and it provides optical signatures that can enable subsequent mechanistic work without the need to label nucleotides. COE-S6-based nanoplexes are thus a promising candidate as nonviral vectors for gene delivery.