Fabrication of aptamer-guided siRNA loaded lipopolyplexes for gene silencing of notch 1 in MDA-mb-231 triple negative breast cancer cell line

Abstract

Triple negative breast cancer is an aggressive type of cancer with limited therapeutic options. Aptamer-functionalized liposomes to deliver short interference RNAs (siRNAs) offer a promising therapeutic option. The current study aimed at preparing an aptamer functionalized liposome loaded with siRNA-protamine polyplexes for selective delivery of Notch 1 siRNA into cancer cells. The aptamer functionalized liposomes were characterized by Dynamic Light Scattering (DLS) and electron microscopy. In vitro silencing and antiproliferative efficiency were conducted using the triple negative breast cancer cell line MDA-MB-231. The unfunctionalized loaded liposomes had a Z-average size of 153.1 ± 6.481 nm and a charge of −17.5 ± 0.265 mV, while the functionalized liposomes had a higher Z-average size of 285 ± 12.33 nm and a charge of −23.8 ± 0.924 mV with an encapsulation efficiency (EE%) of 60%. The presence of the nucleolin aptamer on the surface of the liposomes increased the cellular uptake of liposomes by almost 2 folds. Confocal images showed the co-localization of liposomes and aptamer in the cytoplasm where the siRNA must be released. The functionalized loaded liposomes produced a higher antiproliferative and silencing effect compared to the unfunctionalized liposomes. In conclusion, this formulation represents a novel promising vehicle to deliver siRNA effectively to the MDA-MB-231 cell line.