A Ratiometric Afterglow Luminescence Probe for in Vivo Imaging of Neuroinflammation in Traumatic Brain Injury

The field of traumatic brain injury (TBI) lacks imaging tools capable of monitoring neuroinflammation and oxidative stress. To address this limitation, we developed a ratiometric afterglow nanoparticles (RANPs) by coloading the sensitive afterglow polymer WXS13 with oxidative stress-responsive molecules (ORM) into nanoparticles, establishing an imaging platform capable of precise quantification of reactive oxygen and nitrogen species levels in brain regions affected by TBI. By leveraging afterglow resonance energy transfer (ARET), the nanoprobe exhibited ratiometric signal shifts at 620 and 820 nm upon interaction with inflammatory mediators (specifically ClO – and ONOO – ) in the injured brain, allowing quantitative assessment of oxidative stress levels. Furthermore, this ratiometric afterglow signal showed a positive correlation with the activation of microglia and astrocytes as well as with brain tissue loss. In different degrees of TBI models, RANPs could distinguish mild from severe injury, track spatiotemporal progression of neuroinflammation, and monitor therapeutic responses. This work established a promising afterglow imaging strategy for noninvasive evaluation of ClO – and ONOO – level in TBI models, offering potential for monitoring neuroinflammation and oxidative stress.