Nanoparticle Engineering for Amyotrophic Lateral Sclerosis: Targeted Drug Delivery for Neurodegenerative Diseases

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons, leading to paralysis and eventual respiratory failure. Despite extensive research, effective therapeutic interventions remain elusive, largely due to the challenges posed by the blood-brain barrier (BBB), which restricts drug delivery to the central nervous system (CNS). Nanoparticle-based drug delivery systems offer a promising solution by enabling targeted, sustained, and controlled therapeutic release. This review explores polymeric, lipid-based, inorganic, dendrimer, and exosome-derived nanoparticles, emphasizing advancements such as avidin-associated nucleus-assembled nanoparticles (ANANs) and CRISPR/Cas9-loaded nanocarriers for gene therapy and neuroprotection. Despite their potential, clinical translation faces challenges, including nanoparticle toxicity, immune response activation, scalability, and regulatory constraints. Addressing these barriers requires interdisciplinary research, AI-driven nanoparticle optimization, and large-scale clinical trials. Future innovations integrating nanotechnology, gene editing, and biomolecular engineering hold promise for revolutionizing ALS treatment and accelerating nanoparticle-based therapeutics from bench to bedside.