Exosomes as nanocarriers for brain-targeted delivery of therapeutic nucleic acids: advances and challenges

PMCID: PMC12178025

PMID: 40533746

DOI: 10.1186/s12951-025-03528-2

Journal: Journal of nanobiotechnology

Publication Date: 2025-6-18

Authors: Sanadgol N, Abedi M, Hashemzaei M, Kamran Z, Khalseh R, et al.

Key Points

• Exosomes provide a safer, more controllable alternative to cell-based therapies, eliminating risks like teratoma formation
• Emerging strategies like cell-penetrating peptide conjugation can enhance BBB penetration with up to 90% improved delivery efficiency
• Genetic engineering and advanced cargo loading techniques are critical for developing targeted exosomal therapeutics for neurological disorders

Summary

This comprehensive review explores the emerging potential of exosomes as innovative nanocarriers for nucleic acid-based therapies (NA-BTs) in neurological disorders, addressing the critical challenge of blood-brain barrier (BBB) penetration. By synthesizing recent advances in exosome engineering and drug delivery, the study highlights the transformative potential of these extracellular vesicles in overcoming traditional barriers to neurotherapeutic interventions.

The review demonstrates that exosomes offer significant advantages over conventional drug delivery systems, including superior biocompatibility, natural BBB-crossing capabilities, and the ability to carry therapeutic cargo with minimal immune reactivity. Recent FDA approvals of RNA-based therapies for neurological conditions (such as Patisiran for amyloidosis and Nusinersen for spinal muscular atrophy) underscore the growing clinical relevance of this approach, with exosomes emerging as a promising platform for targeted, precise neurological interventions.