ROS-Responsive Quercetin Nanoparticles Improve the Prognosis of Traumatic Brain Injury by Inhibiting Aberrant...

Area of Science:

• Neuroscience
• Biomaterials Science
• Pharmacology

Background:

• Traumatic brain injury (TBI) is a major cause of death and disability globally, with secondary injury being a key therapeutic target.
• Quercetin (QR), a flavonoid, has shown neuroprotective effects via antioxidant and anti-inflammatory pathways, particularly involving Nrf2-Keap1.
• Poor blood-brain barrier (BBB) permeability and low bioavailability of QR limit its clinical use for brain disorders.

Purpose of the Study:

• To develop a brain-targeted delivery system for quercetin to overcome its pharmacokinetic limitations.
• To investigate the efficacy of quercetin-loaded nanoparticles in mitigating secondary injury following TBI.

Main Methods:

• Network pharmacology identified overlapping targets of quercetin and TBI, emphasizing the Nrf2-Keap1 pathway.
• Developed CAQK peptide-modified, ROS-responsive nanoparticles (C-PPS/Q) for targeted quercetin delivery.
• Evaluated C-PPS/Q in vitro using HT22 cells and in vivo using a TBI mouse model.

Main Results:

• C-PPS/Q demonstrated ROS-triggered quercetin release and enhanced cellular uptake.
• In vitro studies showed reduced ROS levels and apoptosis in HT22 cells treated with C-PPS/Q.
• In vivo, C-PPS/Q accumulated at the TBI lesion site, improved BBB integrity, reduced neuroinflammation, and enhanced neurological function.

Conclusions:

• CAQK peptide-modified, ROS-responsive nanoparticles effectively deliver quercetin to the brain.
• This targeted delivery system mitigates secondary brain injury and improves neurological outcomes in TBI.
• C-PPS/Q nanoparticles represent a promising therapeutic strategy for managing TBI.