Formulation and Quality – Biomolecular
2019 PharmSci 360
Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology in combination with exosomes, a natural vesicles for intercellular communication, for efficient RNAi delivery. By placing membrane-anchoring cholesterol at the tail of the arrow-shape RNA nanoparticles results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. Taking advantage of the RNA ligand for specific targeting and extracellular vesicles for efficient membrane fusion, the resulting ligand-displaying extracellular vesicles were capable of specific delivery of siRNA to cells, and efficiently blocked tumour growth in three cancer models. Extracellular vesicles displaying an aptamer that binds to prostate-specific membrane antigen, and loaded with survivin siRNA, inhibited prostate cancer xenograft. The same extracellular vesicle instead displaying epidermal growth-factor receptor aptamer inhibited orthotopic breast cancer models. Likewise, survivin siRNA-loaded and folate-displaying extracellular vesicles inhibited patient-derived colorectal cancer xenograft.