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 Zn²⁺ 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 Zn²⁺-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 Zn²⁺ 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 Zn²⁺ levels to reveal AD pathogenesis.