Exosomes in Neurodegenerative Disorders: Isolation Strategies, Therapeutic Potential, and Clinical Trials.
Exosomes represent a promising class of naturally produced nanoparticles that exist at the nanoscale and carry a negative surface charge under physiological conditions. These tiny membranebound vesicles are released by cells throughout the body and function as biological messengers, transporting various molecular cargos between cells and facilitating critical cell-to-cell communication pathways. Existing therapies for neurodegenerative disorders face two critical barriers: they cannot precisely target the affected brain areas, and the blood-brain barrier blocks most potential treatments from entering the brain. Exosomes offer a promising solution to these challenges. Unlike most synthetic drug delivery systems that struggle to penetrate the brain's protective barrier, these naturally derived nanocarriers exhibit an inherent capacity to traverse the blood-brain barrier. This unique property, combined with their capacity for efficient intracellular delivery of therapeutic payloads, positions exosomes as an exciting platform for transporting pharmaceutical agents to the affected neural tissues. Through strategic engineering and modification, these vesicles can be transformed into highly precise delivery vehicles capable of targeting specific organs, tissues, or even individual cell types. This review explores the therapeutic potential and drug delivery applications of exosomes in the management of major neurodegenerative disorders. This review provides an in-depth examination of exosome biogenesis, current isolation methodologies, and surface engineering strategies, while critically evaluating the strengths and limitations of each approach. In addition, this review summarizes the current preclinical models and provides an overview of ongoing clinical trials investigating exosome-based therapies for neurological disorders.