Advances in Nanotechnology - Engineered Exosomes for Early Biomarker Detection and Therapy in Alzheimer’s Disease

Abstract

Advances in the understanding of exosome biology have led to their recognition as the heart of intercellular communications. Additionally, the new insights into the role of exosomes in neuroinflammation and spreading of characteristic Alzheimer’s Disease (AD) pathologies, open the scope for their use as a key target for diagnostic and therapeutic innovation. The immuno-engineering platforms are sensitive for detecting exosomal biomarkers including amyloid-β species, phosphorylated tau, and regulatory microRNAs, in peripheral biofluids with minimal invasion. Hence, these are potential platforms that can facilitate early diagnosis of AD. Although most supporting evidence is presently derived based on preclinical models and limited observational cohorts, these findings support minimally invasive opportunities for early disease monitoring and diagnosis, possibly even before the manifestation of clinical symptoms of AD. Alongside, another advantage of engineered exosomes is their flexible framework for targeted drug delivery. Since engineered exosomes are derived from neuronal or mesenchymal stem cells, they can cross the blood-brain barrier and deliver neuroprotective or immunomodulatory agents with high specificity. Presently, the target precision and off-target biodistribution of engineered exosomes are one of the most active areas of investigation. More encouragingly, incorporating nanotechnology for surface modification and cargo loading strategies can further enhance exosomal signaling, delivery efficiency, and cell-specific uptake by neuronal and glial cells. These applications, however, are presently challenging in terms of scalability and reproducibility. Also, a number of advancements are needed in areas of standardization of exosome isolation, scalable manufacturing, regulatory frameworks, and biological heterogeneity. Overcoming these challenges, however, is feasible with the integration of Artificial Intelligence and multi-omics profiling, and optimisation of exosome-based interventions.