Screening Anti-Parkinson’s Disease Drugs in\nLiving Mouse Brains via a Peroxynitrite-Activated Fluorescent Probe

Screening anti-Parkinson’s\ndisease (PD) drugs at <i>in vivo</i> brain level is imperative\nfor managing PD yet currently\nremains unaccomplished. Peroxynitrite (ONOO<sup>–</sup>) has\nbeen implicated in PD progression. Thus, developing <i>in vivo</i> ONOO<sup>–</sup>-based imaging tools for anti-PD drug screening\nholds promise for early prognosis and treatment of PD. Consequently,\na near-infrared (NIR) fluorescence probe, <b>BOB-Cl-PN</b>,\nwith high specificity, good sensitivity (LOD = 24 nM), and rapid response\n(<60 s), was devised to investigate ONOO<sup>–</sup> and\nPD relationships. Utilizing NIR fluorescence imaging, <b>BOB-Cl-PN</b> effectively monitored ONOO<sup>–</sup> fluctuations in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine\n(MPTP)-induced PD cell models, establishing a cellular high throughput\nscreening (cHTS) system for anti-PD drugs. In live animal imaging, <b>BOB-Cl-PN</b>’s ability to penetrate the blood–brain\nbarrier enabled ONOO<sup>–</sup> flux imaging of PD mouse brains.\nMoreover, <b>BOB-Cl-PN</b> served as an imaging contrast for <i>in vivo</i> screening of potential traditional Chinese medicines\nfor PD therapy, identifying fisetin as having the best therapeutic\nindex among 10 Chinese medicines. This study constructs a sensitive,\nefficient imaging contrast for monitoring ONOO<sup>–</sup> dynamics\nin PD brains and provides a valuable platform for cellular and <i>in vivo</i> screening of anti-PD drugs.