Small-Molecule Fluorophores for Near-Infrared IIb Imaging and Image-Guided Therapy of Vascular Diseases

Abstract

Accurate and dynamic visualization of vascular diseases can contribute to restraining the further deterioration of diseases in a timely manner. However, it is still unable to precisely determine whether and to what extent blood vessels or brain tissues are damaged. Here we report novel BBTD-based NIR-II fluorophores HY1-HY4 with highly twisted structures (55 o at the S 0 state), extremely strong aggregation-induced emission (AIE) characteristics (I/I 0 > 13), and remarkably high fluorescence QYs (up to 14.45%) in the NIR-II region (> 1000 nm) and ~ 0.27% in the NIR-IIb window (> 1500 nm) in aqueous solution. Using NIR-IIb AIE HY4 dots, high-resolution NIR-IIb fluorescence imaging of revascularization and thrombolysis, and real-time feedback of the therapeutic efficacy of Chinese medicine DXI on ischemic stroke, were achievedfor the first time. In addition, results showed that DXI conferred neuroprotection against cerebral ischemia injury mediated via the angiogenesis pathway. These attractive results provide a new perspective for designing ultra-bright NIR-IIb probes for the vascular-related phenomena, disease assessment, and precise intraoperative imageguided therapy with a deeper tissue penetration depth and higher resolution.

Rational Design of NIR-II AIEgens with Ultrahigh Quantum Yields for Photo- and Chemiluminescence Imaging

“…Aggregation-induced emission (AIE) is a unique photophysical phenomenon where AIE-active molecules are nonemissive or weakly emissive in the discrete state because of active intramolecular motions, but show enhanced luminescence upon aggregation due to mechanisms including the restriction of intramolecular motions (RIM), restricted access to a conical intersection, and restriction of access to the dark state. − Various AIE luminogens (AIEgens) have been developed and have shown great potential for biomedical applications. − In NIR-II bioimaging, the AIE strategy is also promising. Many NIR-II AIEgens with acceptable QYs can act as superior imaging materials (the highest QY approaches 15% using IR26 as the reference fluorophore with a QY of 0.5% in 1,2-dichloroethane). ,− For instance, our group reported TPA-BBT in 2019, which contained the electron donor triphenylamine (TPA) and acceptor benzobisthiadiazole (BBT) (Figure a). The nanoparticle of TPA-BBT demonstrated a very high QY of about 11% in water .…”

The pursuit of polymethine fluorophores with NIR-II emission and high brightness forin vivoapplications

“…NIR-II bioimaging technique can clearly discriminate the anatomical structures (e.g., tumor, vasculature, lymph nodes, and skeleton) and monitor the dynamic physiological processes (e.g., blood perfusion, ischemia, and arterial thrombosis) owing to its high temporal and high spatial resolution and deep tissue penetration. 58,63 NIR-II polymethine uorophores have been successfully applied in tumor imaging in vivo, showing great penetration depth, outstanding spatial resolution, and high signal-to-noise ratio. For example, the polymethine thiopyrylium salt 5H5 has both absorption and emission in the NIR-II window with a maximum absorption at 1069 nm and maximum emission at 1125 nm.…”

Bichromatic Imaging with Hemicyanine Fluorophores Enables Simultaneous Visualization of Non-alcoholic Fatty Liver Disease and Metastatic Intestinal Cancer

“…Fluorescence imaging in the near-infrared region (NIR-I: 700–900 nm, NIR-II: 1000–1700 nm) has great potential for improving disease diagnosis due to its high sensitivity, good spatiotemporal resolution, and noninvasive visualization, especially in the NIR-II window, providing higher spatial resolution and deeper in vivo tissue penetration because of reduced photon scattering and autofluorescence. − Hence, smart activatable NIR fluorescent probes that can respond to biomarkers and cellular microenvironment are promising for early and accurate diagnosis of NAFLD and metastatic intestinal cancer. − As an important microenvironmental parameter, intracellular viscosity plays a crucial role in signal transduction, biological species diffusion, and cell metabolism. , Nevertheless, abnormal changes in viscosity in cells are closely related to different diseases, such as atherosclerosis, diabetes, and Alzheimer’s disease. , Moreover, cytoplasmic viscosity increase is also an essential physiological feature of NAFLD. , Viscosity-responsive fluorophores with a molecular rotor have been recently reported to monitor intracellular viscosity variations. − Unfortunately, because of the short emission wavelength and high background fluorescence, these fluorescent probes were mainly applied in monitoring viscosity in live cells, and there was no viscosity-responsive NIR-II fluorophore for early detection of NAFLD in living animals. On the other hand, low extracellular pH (6.5–6.8) is a cancer hallmark that plays an important role in tumor proliferation, invasion, and metastasis .…”