Microbubbles in combination with focused ultrasound to deliver Quercetin-modified sulfur nanoparticles: through the blood brain barrier into the brain parenchyma and relieve endoplasmic reticulum stress to treat Alzheimer's disease
Delivering the drugs to cross the blood-brain barrier (BBB) effectively and safely is one of the major challenges in the treatment of neurodegenerative diseases. In this work, we constructed a nano-system that used microbubbles to promote drug cross BBB, microbubbles in combination with focused ultrasound were used to mediate BBB transient opening and delivery of nanomedicines. This system (Qc@SNPs-MB) was formed by Quercetin-modified nanosulfur (Qc@SNPs) embedded into microbubbles (MB). Qc@SNPs-MB would be destroyed instantly when it was exposed to ultrasonic pulses, and it would enhance the permeability of the blood vessels and cause a brief opening of the BBB owing to the “sonoporation” effect. And Qc@SNPs were released from the outer shell of the microbubbles and enter the brain across the open BBB, accumulating in the brain parenchyma. Due to the rapid accumulation of Qc@SNPs in the brain, it effectively reduced neuronal apoptosis，inflammatory response, calcium homeostasis imbalance, and oxidative stress all mediated by endoplasmic reticulum stress, and protected nerve cells, thus treating Alzheimer's disease (AD) effectively. Morris water maze experiment showed that the learning ability and memory ability of AD mice treated with Qc@SNPs were significantly improved, and no obvious side effect were found. Therefore, Qc@SNPs-MB in combined with ultrasound provide an effective and safe drug deliver method for the treatment of neurodegenerative diseases and a promising strategy for endoplasmic reticulum stress therapy.