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Reprograming Clots for In Vivo Chemical Targeting in Traumatic Brain Injury
Rebecca M Kandell1, Jason R Wu1, Ester J Kwon1
1Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.
Advanced Materials (Deerfield Beach, Fla.)
|May 23, 2024
Summary
Researchers developed a novel chemical targeting method to improve drug delivery to traumatic brain injuries (TBI). This approach utilizes the brain's natural clot formation to enhance therapeutic retention and efficacy.
Area of Science:
- Biomedical Engineering
- Neuroscience
- Drug Delivery
Background:
- Traumatic brain injury (TBI) presents significant challenges for therapeutic intervention due to the blood-brain barrier and increased intracranial pressure.
- Current treatments for TBI lack options to improve long-term patient outcomes, highlighting the need for innovative drug delivery strategies.
Purpose of the Study:
- To develop and validate a chemical targeting strategy for enhanced drug delivery to the injured brain.
- To leverage the provisional fibrin matrix formed at the injury site as a scaffold for targeted material delivery using click chemistry.
Main Methods:
- Engineered the in situ brain clot by delivering modified fibrinogen with strained cyclooctyne (SCO) moieties.
- Utilized click chemistry to attach azide-modified materials (dye, nanomaterial, protein) to the SCO-fibrinogen scaffold within the TBI lesion.
- Administered the antioxidant catalase to assess therapeutic translation and measured reactive oxygen species (ROS) levels.
Main Results:
- Demonstrated improved capture and retention of various azide-materials within the TBI lesion for extended periods.
- Confirmed specific colocalization of targeted materials within the brain injury site, with minimal off-target accumulation.
- Achieved a reduction in ROS levels in the injured brain following catalase delivery, indicating therapeutic efficacy.
Conclusions:
- Established a chemical targeting strategy that utilizes endogenous clot formation to improve therapeutic delivery after TBI.
- This approach shows potential for enhancing the efficacy of treatments for traumatic brain injuries.
- The method offers a promising avenue for overcoming drug delivery challenges in TBI.
