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Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System
Mena Asha Krishnan1,2, Olawale A Alimi1,2, Tianshu Pan1,2
1Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Pharmaceutics
|January 23, 2024
Summary
Engineered red blood cell-derived exosomes (Exos) carrying tetanus toxin-C fragment (TTC) show improved delivery to peripheral nerve targets. This novel exosome system enhances therapeutic potential for peripheral neuropathies.
Area of Science:
- Biotechnology
- Neuroscience
- Drug Delivery
Background:
- Peripheral nerve drug delivery faces challenges due to complex anatomy and the blood-nerve barrier.
- Erythrocyte-derived exosomes (Exos) are promising biocompatible carriers, but targeting the peripheral nervous system (PNS) remains difficult.
Purpose of the Study:
- To develop a targeted exosome delivery system for presynaptic terminals in peripheral nerve tissue.
- To engineer red blood cell (RBC)-derived exosomes with tetanus toxin-C fragment (TTC) for enhanced peripheral nerve targeting.
Main Methods:
- Tetanus toxin-C fragment (TTC) and Cyanine5 (Cy5) fluorescent tag were conjugated to RBC-derived exosomes using bio-orthogonal click chemistry.
- In vitro studies used Neuro-2a neuronal cells to assess TTC-exosome accumulation.
- In vivo studies utilized a mouse model to track intramuscularly administered TTC-exosomes in sciatic nerve tissue.
Main Results:
- TTC-conjugated exosomes (TTC-Exos) demonstrated significantly higher accumulation in neuronal cells compared to unmodified exosomes.
- In vivo, engineered TTC-Exos were successfully delivered to neuromuscular junctions and sciatic nerve tissues within 72 hours.
- TTC conjugation was crucial for enhancing the affinity and delivery of exosomes to peripheral nerve targets.
Conclusions:
- Engineered TTC-Exos represent a viable strategy for targeted therapeutic delivery to the peripheral nervous system.
- This approach holds significant potential for treating peripheral neuropathies by overcoming delivery barriers.
- The study highlights the efficacy of bio-orthogonal chemistry in creating functionalized exosomes for neural applications.
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