Crossing Barriers: PEGylated Gold Nanoparticles as Promising Delivery Vehicles for siRNA Delivery in Alzheimer’s Disease

<b>Background</b>: The proportion of people suffering from neurodegenerative conditions, such as Alzheimer's disease (AD), is increasing in the population year on year. Despite the constant effort of researchers, these conditions remain incurable and can only be managed by alleviation or delaying of symptoms. The lack of suitable treatment is caused by constricted access to the brain, limited by the brain-blood barrier. The aim of this work was to investigate two pegylated gold nanoparticles as potential carriers of therapeutic siRNA and their impact on the cellular functions of Human Brain Endothelial Cells. <b>Methods and Results</b>: Nanoparticles AuNP14a and AuNP14b complexed with siRNA were internalized by HBEC-5i cells and located in the cytoplasm. The genotoxicity assay proved that the nucleus was not affected and complexed nanoparticles did not cause DNA damage. The reactive oxygen species formation and mitochondrial membrane potential changes were measured and showed an adaptive response of cells after compound administration. Results obtained in a cytotoxicity assay conducted on astrocytes and pericytes, which are components of the blood-brain barrier, confirmed the biosafety of tested nanoparticles. <b>Conclusions</b>: In summary, it was shown that AuNP14a and AuNP14b are promising candidates as nanocarriers for therapeutic nucleic acids through biological barriers.