Photostable Small-Molecule NIR-II Fluorescent Scaffolds that Cross the Blood-Brain Barrier for Noninvasive Brain Imaging

The second near-infrared (NIR-II, 1000-1700 nm) fluorescent probes have significant advantages over visible or NIR-I (600-900 nm) imaging for both depth of penetration and level of resolution. Since the blood-brain barrier (BBB) prevents most molecules from entering the central nervous system, NIR-I...

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Published in:Journal of the American Chemical Society Vol. 144; no. 51; pp. 23668 - 23676
Main Authors: Wang, Shichao, Shi, Hui, Wang, Lushun, Loredo, Axel, Bachilo, Sergei M., Wu, William, Tian, Zeru, Chen, Yuda, Weisman, R. Bruce, Zhang, Xuanjun, Cheng, Zhen, Xiao, Han
Format: Journal Article
Language:English
Published: WASHINGTON Amer Chemical Soc 28.12.2022
Subjects:
Animals
Blood-Brain Barrier
Brain - diagnostic imaging
Chemistry
Chemistry, Multidisciplinary
Fluorescent Dyes
Mice
Neoplasms
Neuroimaging
Optical Imaging - methods
Physical Sciences
Science & Technology
SURGERY
MODALITY MRI
TUMORS
DELIVERY
ISSN:0002-7863, 1520-5126, 1520-5126
Online Access:Get more information
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Summary:The second near-infrared (NIR-II, 1000-1700 nm) fluorescent probes have significant advantages over visible or NIR-I (600-900 nm) imaging for both depth of penetration and level of resolution. Since the blood-brain barrier (BBB) prevents most molecules from entering the central nervous system, NIR-II dyes with large molecular frameworks have limited applications for brain imaging. In this work, we developed a series of boron difluoride (BF2) formazanate NIR-II dyes, which had tunable photophysical properties, ultrahigh photostability, excellent biological stability, and strong brightness. Modulation of the aniline moiety of BF2 formazanate dyes significantly enhances their abilities to cross the BBB for noninvasive brain imaging. Furthermore, the intact mouse brain imaging and dynamic dye diffusion across the BBB were monitored using these BF2 formazanate dyes in the NIR-II region. In murine glioblastoma models, these dyes can differentiate tumors from normal brain tissues. We anticipate that this new type of small molecule will find potential applications in creating probes and drugs relevant to theranostic for brain pathologies.
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ISSN:0002-7863
1520-5126
1520-5126
DOI:10.1021/jacs.2c11223