Activatable NIR-IIb Nanosensor for Visualizing Brain HClO to Monitor Parkinson's Disease.

Area of Science:

• Biomedical Engineering
• Neuroscience
• Chemical Biology

Background:

• Parkinson's disease (PD) diagnosis relies on subjective assessments, hindering early detection and treatment.
• Hypochlorous acid (HClO) is a key reactive oxygen species implicated in PD pathogenesis.
• There is a need for objective biomarkers to monitor PD progression and therapeutic responses.

Purpose of the Study:

• To develop a highly sensitive and specific fluorescent probe for detecting cerebral hypochlorous acid (HClO) in Parkinson's disease (PD).
• To enable real-time in vivo monitoring of PD progression and drug efficacy using advanced imaging techniques.
• To overcome the limitations of subjective clinical assessments in PD diagnosis and management.

Main Methods:

• Design and synthesis of a novel HClO-activated NIR-IIb fluorescent probe (SQ6-RENPs) utilizing rare-earth nanoparticles (RENPs) and a VHP peptide.
• Utilizing an absorption competition-induced emission (ACIE) mechanism for modulated NIR-IIb emission.
• In vivo evaluation in Parkinson's disease model mice, assessing blood-brain barrier (BBB) penetration, cerebral HClO detection, and therapeutic response monitoring.

Main Results:

• The SQ6-RENPs probe demonstrated high sensitivity, selectivity, and stability for detecting HClO under physiological conditions.
• The VHP peptide facilitated efficient blood-brain barrier (BBB) crossing and brain accumulation of the probe.
• In vivo imaging successfully visualized PD severity and evaluated drug efficacy by real-time monitoring of cerebral HClO levels in PD model mice.

Conclusions:

• SQ6-RENPs offers a promising tool for objective and accurate Parkinson's disease diagnosis.
• The probe provides a novel strategy for accelerated drug evaluation in preclinical PD research.
• This approach represents a significant advancement in neurodegenerative disease monitoring and therapeutic development.