posted on 2022-12-21, 16:05authored byQinyu Wang, Jing Zhong, Kexin Li, Jiajun Wu, Xiaoxue Wang, Shen Jiang, Jiapei Dai, Yan Cheng
Protein
aggregation has been found in a wide range of neurodegenerative
protein-misfolding diseases. The demand for in vivo technologies to
identify protein aggregation is at the leading edge for the pathogenic
study, diagnostic development, and therapeutic intervention of these
devastating disorders. Herein, we report a series of luminol analogues
to construct a facile chemiluminescence (CL)-based approach for in
vivo detection and imaging of β-sheet protein aggregates. The
synthesized compounds exhibited a distinct chemiluminescent response
with long emission wavelengths toward reactive oxygen species under
physiological conditions and displayed signal amplification in the
presence of β-sheet protein aggregates, including α-synuclein,
β-amyloid, and tau. Among them, CyLumi-3 was further
evaluated as a chemiluminescent probe in preclinical models. By intravenous
administration into the model mice via the tail vein, in vivo CL imaging
noninvasively detected the specific CL of the probe targeting the
α-synuclein aggregates in the brains of living mice. Based on
its structural characteristics, CyLumi-3 can readily
interact with α-synuclein aggregates with significantly enhanced
fluorescence and can identify α-synuclein aggregates in vivo
via distinctive CL amplification, which could pave the way for a more
comprehensive understanding of protein aggregation in preclinical
studies and would provide new hints for developing small-molecule
chemiluminophores for protein aggregates.