​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 …​