Turn-On NIR-II Polymer Dots with Large Stokes Shift for In Vivo Visualizing Dynamical Brain Zinc in Alzheimer's Disease Mouse.

It is a critical and broad prospect to evaluate ion levels and monitor their dynamic changes in the brain for early diagnosis, in-depth mechanism investigation, and accurate staging of neurodegenerative diseases including Alzheimer's disease (AD). It is still a great challenge to in vivo track Zn levels in the brain by fluorescence imaging due to the drawbacks including short emission wavelength, poor selectivity and sensitivity, and unfavorable penetration across the blood-brain barrier (BBB) for currently developed fluorescent probes. We herein engineer a fluorescent probe with a large Stokes shift of 256 nm, NNDPTQ Pdots, which display substantial Zn-specific turn-on response in the NIR II region with the longest emission of 1064 nm up to now. The probe shows a fast response within seconds, high selectivity, low-nanomolar affinity of 6 nM, low detection limit of 3.4 nM, and efficient BBB-permeability efficacy of 37%. The results of brain imaging demonstrate that brain Zn level in AD mice is substantially higher than normal mice and also is elevated with the prolonging of AD-bearing time. This study may provide a promising fluorescent indicator for in vivo tracing of brain Zn levels to reveal AD pathogenesis.