Engineered Exosomes in Precision Neuro-Oncology: Mechanisms, Therapeutics, and Translational Challenges

Area of Science:

• Biotechnology
• Neuroscience
• Drug Delivery

Background:

• Exosomes, small vesicles released by cells, are explored as drug delivery vehicles for brain diseases.
• Conventional methods face challenges like immune clearance and poor brain accumulation.
• Engineered exosomes leverage natural mechanisms to cross the blood-brain barrier (BBB) and interact with target cells.

Purpose of the Study:

• To review the mechanistic and translational aspects of engineering exosomes for central nervous system (CNS) disorders, focusing on glioblastoma.
• To discuss exosome biogenesis, secretion, and degradation pathways influencing therapeutic production.
• To explore cargo loading and surface modification strategies for targeted delivery.

Main Methods:

• Review of exosome biogenesis (ESCRT-dependent/independent pathways) and secretion/degradation dynamics (Rab27/Rab7).
• Analysis of genetic, physical (electroporation, sonication), and surface modification methods for exosome engineering.
• Examination of engineered exosome applications in glioblastoma, stroke, and neurodegenerative diseases.

Main Results:

• Engineered exosomes show promise in delivering therapeutics across the BBB for glioblastoma, targeting glioma stem cells, and enabling gene editing.
• Preclinical studies demonstrate encouraging results for engineered exosomes in stroke and neurodegenerative diseases using microRNAs and neuroprotective cargo.
• Challenges in scalable manufacturing and consistent targeting are being addressed by emerging approaches.

Conclusions:

• Engineered exosomes represent a viable platform for CNS drug delivery, moving from concept to practical application.
• Further development in scalable production and targeting strategies is crucial for clinical translation.
• The review highlights the potential of engineered exosomes for treating complex brain disorders.