Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease

Identification of pharmacological and toxicological profiles is of critical importance for the use of nanoparticles as drug carriers in nanomedicine and for the bio-safety evaluation of environmental nanoparticles in nanotoxicology. Here we show that lysosomes are the pharmacological target organelles and mitochondria are the toxicological organelles of SWCNT. The gastrointestinally absorbed SWCNT were lysosomotropic but also entered mitochondria at large doses. III PI3K and LAMP-2A genes was involved in such an organelle preference. SWCNT resulted in collapse of mitochondrial membrane potentials, giving rise to overproduction of ROS, leading to damage of mitochondria, which was followed by lysosomal and cellular injury. Based on the dosage differences in target organelles, SWCNT were successfully used to deliver acetylcholine into brain for treatment of Alzheimer’s disease with rather high safety range by well controlling the doses, which ensures SWCNT only enter lysosomes, the pharmacological organelles, and no or less enter mitochondria, the toxicological organelles.