Project R-13488

Extracellular vesicle-coated responsive nanocarriers for targeted stroke therapy (Research)

Stroke is a devastating neurological condition caused by loss of brain tissue and function due to interrupted or severely impaired blood flow to the brain. Worldwide, stroke is classified as leading cause of adult disability and second leading cause of mortality. In ischemic stroke, which covers 85% of all stroke cases, available treatments are only eligible in 7-13% of patients, with the majority having residual neurological impairments. In stroke pathology, depletion of blood supply to the brain leads to severe oxygen and glucose deprivation, followed by mitochondrial dysfunction, and eventual depletion of ATP and overproduction of ROS. ROS-release starts a cascade of pathophysiological events in the brain, e.g. cell death, blood-brain barrier disruption, edema formation and inflammation. In addition, on-site activation of immune cells leads to the production of cytokines and more ROS, making ROS a key molecule in stroke pathology. Targeting neuroinflammation is promising but difficult due to drug-induced emetic effects. Therefore, over the years, nanocarriers made of biopolymers, have received a lot of attention because of their advantages in terms of drug stabilization, side effects reduction and improved drug pharmacokinetic and -dynamic profiles. Nevertheless, uncontrolled drug release and non-specific biodistribution remain a major concern. To overcome these hurdles, this project aims to synthesize nanocarriers responsive to the stroke environment, i.e. stroke pathology's key molecule ROS, and provide them of a bio-inspired coating, i.e. biocompatible, non-immunogenic and blood-brain barrier-crossing extracellular vesicles. Generation of such 'nanohybrids' is hypothesized to lead to major advancement in safe and efficacious drug delivery.

14 December 2022 - 31 October 2028