Exosome Therapy in Alzheimer's Disease: A Nanobiotechnology Approach – Next-Generation Therapeutic Opportunities

Abstract

Alzheimer’s disease (AD) remains one of the most formidable neurodegenerative challenges of the 21st century, characterized by progressive cognitive decline, extracellular amyloid-beta (Aβ) plaque deposition, and intracellular neurofibrillary tangles of hyperphosphorylated tau. Traditional pharmacological interventions struggle to achieve therapeutic efficacy, primarily due to their inability to cross the highly restrictive blood-brain barrier (BBB) and their lack of cell-specific targeting. Nanobiotechnology has emerged as a transformative paradigm, leveraging engineered extracellular vesicles—specifically exosomes—as next-generation drug delivery systems. As natural nano-shuttles (30–150 nm), exosomes possess inherent biocompatibility, low immunogenicity, and the capacity to cross biological membranes. This review comprehensively synthesizes the nanobiotechnology foundations of exosome engineering, exploring advanced methods for therapeutic cargo loading (including small molecules, proteins, and RNA-based therapies) and surface functionalization strategies aimed at enhancing brain tropism. We critically evaluate preclinical and emerging clinical evidence of exosome-mediated interventions targeting key AD pathological hallmarks: Aβ clearance, tau phosphorylation cascades, chronic neuroinflammation, and synaptic loss. Finally, we address the formidable obstacles to clinical translation, including scalable manufacturing, standardized isolation protocols, regulatory frameworks, and long-term safety profiles, outlining a strategic roadmap for the realization of exosome-based nanomedicine in AD therapeutics.