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

Abstract

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.

Homotypic Membrane-Enhanced Blood–Brain Barrier Crossing and Glioblastoma Targeting for Precise Surgical Resection and Photothermal Therapy

“…In order to evaluate the BBB crossing ability of GBM-PDTCM@AuNRs, an in vitro BBB model was built on a transwell system (Figure D), in which an immortalized mouse brain endothelial (bEnd.3) cell monolayer was seeded on the bottom of the upper chamber, mimicking the BBB, and U-87 MG cells were cultured in the 24-well plate, representing the GBM tissue. As displayed in Figure S9, the transendothelial electrical resistance of the bEnd.3 cell monolayer is 1000 Ω·cm 2 , indicating the high density of endothelial cells, which meets the requirement of building an in vitro BBB model .…”

Molecular Design of NIR-II Polymethine Fluorophores for Bioimaging and Biosensing

“…Because pathological changes in the brain are often fatal to organisms, the diagnosis and treatment of the brain are essential. Up to date, only a few fluorophores and drugs could cross the blood-brain barrier to perform imaging diagnosis and accurate treatment . An ideal small molecular NIR-II fluorophore for noninvasive brain imaging is stable, bright, and especially has proper molecular size.…”

Optical and Photoacoustic Imaging In Vivo: Opportunities and Challenges

“…Optical imaging has emerged as one of the effective instruments for disease diagnosis benefiting from its noninvasiveness, high sensitivity, and timeliness. However, traditional optical imaging relies on the fluorescence in the visible region, which is unsuitable for biomedical applications due to the strong light–tissue interactions like scattering and reabsorption . It is urgent to develop optimized nanoprobes with longer emission wavelengths to reduce the background interference and improve the quality of optical imaging.…”

“…However, traditional optical imaging relies on the fluorescence in the visible region, which is unsuitable for biomedical applications due to the strong light−tissue interactions like scattering and reabsorption. 5 It is urgent to develop optimized nanoprobes with longer emission wavelengths to reduce the background interference and improve the quality of optical imaging. Further, photoacoustic (PA) imaging integrated optical imaging with ultrasound (US) imaging possesses the ability of improving tissues penetration for the "laser input, acoustic wave output" characteristic of PA imaging.…”