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Design of an activatable NIR-II nanoprobe for the in vivo elucidation of Alzheimer's disease-related variations in methylglyoxal concentrations† † Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2sc05242c


ABSTRACT: Clear elucidation of the changes in Alzheimer's disease (AD)-related methylglyoxal (MGO) levels in vivo is significant yet highly challenging. Fluorescence imaging in the second near-infrared region (NIR-II, 1000–1700 nm) has gained increasing attention as an observation method in living organisms, but an MGO-activatable fluorescent probe that emits in this region for in vivo brain imaging is lacking because of the existence of the blood–brain barrier (BBB). Herein, a biocompatible Fe3O4 nanoparticle (IONP)-conjugated MGO-activatable NIR-II fluorescent probe (MAM) modified with the peptide T7 (HAIYPRH) (named TM-IONP) is reported for the in situ detection of MGO in a transgenic AD mouse model. In this system, the T7 peptide enhances BBB crossing and brain accumulation by specifically targeting transferrin receptors on the BBB. Due to the MAM probe, TM-IONPs emit fluorescence in the NIR-II region and display high selectivity with an MGO detection limit of 72 nM and a 10-fold increase in the fluorescence signal. After intravenous administration, the TM-IONPs are easily delivered to the brain and pass through the BBB without intervention, and as a result, the brains of AD mice can be noninvasively imaged for the first time by the in situ detection of MGO with a 24.2-fold enhancement in NIR-II fluorescence intensity compared with wild-type mice. Thus, this MGO-activated NIR-II-emitting nanoprobe is potentially useful for early AD diagnosis in clinic. A biocompatible Fe3O4 nanoparticle integrating methylglyoxal-activatable NIR-II fluorescent probe and brain-targeting peptide was developed for visualizing Alzheimer's disease (AD)-related methylglyoxal variation in vivo.

SUBMITTER: Lai Y 

PROVIDER: S-EPMC9628982 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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