Microfluidic Platforms for Exosome Engineering: Scalable Therapeutics for Cancer Immunotherapy and Infectious...

Area of Science:

• Biotechnology
• Nanomedicine
• Immunotherapy

Background:

• Extracellular vesicles (EVs), especially exosomes, show therapeutic promise due to biocompatibility and targeting.
• Traditional exosome production methods face challenges with low yield, reproducibility, and stability.
• Microfluidics offers precise, automated, and low-shear manipulation to overcome these limitations.

Purpose of the Study:

• To review recent advancements in microfluidic-engineered exosomes for cancer immunotherapy and infectious diseases.
• To evaluate microfluidic strategies for exosome isolation, surface engineering, and cargo loading.
• To address the scalability challenges and future directions for clinical translation.

Main Methods:

• Review of microfluidic platforms including ExoArc, acoustofluidics, cellular nanoporation, and electroporation.
• Focus on advanced modalities like immune cell-derived exosomes (IEX), neo-antigen presentation, CAR-exosomes, and siRNA delivery.
• Analysis of technological gaps between analytical and manufacturing scales, considering protein stability.

Main Results:

• Microfluidics enables precise engineering of exosomes for enhanced therapeutic applications.
• Specific platforms and modalities are evaluated for their potential in cancer and infectious disease treatment.
• Potential damage to surface proteins during scale-up is identified as a critical concern.

Conclusions:

• Microfluidic engineering is crucial for developing standardized, clinical-scale, cell-free immunotherapies.
• Future directions include high-throughput systems, scarless elution, and integrated 'sample-to-therapy' circuits.
• Adherence to MISEV2023 guidelines is essential for clinical translation.