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Targeting peptide homes to spinal cord injury in a rat model

BACKGROUND CAQK (cysteine-alanine-lysine glutamine) is a homing peptide shown to selectively target injured regions of the brain. This study evaluated CAQK in a rodent model of spinal cord injury (SCI) to determine its localization capacity, dose-response characteristics, and temporal binding properties. METHODS This is a preclinical pharmacology study of a nanotherapeutic drug delivery system. Twenty-four adult rats underwent C6 right-sided spinal cord hemicontusion. Animals received a tail vein injection of cyanine5-labeled CAQK (CAQK-Cy5) at low (0.5 mg/kg), medium (1.0 mg/kg), or high dose (2.5 mg/kg) or matched doses of free Cy5 dye as a control (n = 3 per group). Localization was monitored via in vivo fluorescence imaging at 1 and 24 hours in all animals and up to 7 days in an additional cohort of high-dose CAQK-Cy5 and Cy5 animals. Spinal cords were harvested for ex vivo imaging and histological confirmation of CAQK-Cy5 accumulation. RESULTS In vivo imaging demonstrated CAQK-Cy5

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Study findings do not automatically establish clinical benefit, safety, dosing, or suitability for an individual.

BACKGROUND

CAQK (cysteine-alanine-lysine glutamine) is a homing peptide shown to selectively target injured regions of the brain. This study evaluated CAQK in a rodent model of spinal cord injury (SCI) to determine its localization capacity, dose-response characteristics, and temporal binding properties.

METHODS

This is a preclinical pharmacology study of a nanotherapeutic drug delivery system. Twenty-four adult rats underwent C6 right-sided spinal cord hemicontusion. Animals received a tail vein injection of cyanine5-labeled CAQK (CAQK-Cy5) at low (0.5 mg/kg), medium (1.0 mg/kg), or high dose (2.5 mg/kg) or matched doses of free Cy5 dye as a control (n = 3 per group). Localization was monitored via in vivo fluorescence imaging at 1 and 24 hours in all animals and up to 7 days in an additional cohort of high-dose CAQK-Cy5 and Cy5 animals. Spinal cords were harvested for ex vivo imaging and histological confirmation of CAQK-Cy5 accumulation.

RESULTS

In vivo imaging demonstrated CAQK-Cy5 signal at the SCI site within 1-hour postinjection, which persisted up to 7 days in the high-dose group. Signal intensity was dose dependent and declined over time. No significant localization was observed in control animals or uninjured spinal regions.

CONCLUSION

CAQK rapidly and selectively localizes to injured spinal cord tissue in a dose-responsive manner, with peak accumulation observed within 24 hours. These findings support its potential as a targeted delivery vector for injectable therapeutics in acute SCI.

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