Rational Design of a Two‐Photon Fluorogenic Probe for Visualizing Monoamine Oxidase A Activity in Human Glioma Tissues

Abstract

Monoamine oxidases have two functionally distinct but structurally similar isoforms (MAO‐A and MAO‐B). The ability to differentiate them by using fluorescence detection/imaging technology is of significant biological relevance, but highly challenging with available chemical tools. Herein, we report the first MAO‐A‐specific two‐photon fluorogenic probe (F1), capable of selective imaging of endogenous MAO‐A enzymatic activities from a variety of biological samples, including MAO‐A‐expressing neuronal SY‐SY5Y cells, the brain of tumor‐bearing mice and human Glioma tissues by using two‐photon fluorescence microscopy (TPFM) with minimal cytotoxicity.

Recent advances in construction of small molecule-based fluorophore-drug conjugates

“…Most triggers are specifically overexpressed in subcellular organelles. For examples, enzymes like nitroreductase, monoamine oxidases [ 84 , 85 ] and cytochrome C, the same as ROSs, are overexpressed in mitochondria. In addition, hydrophobic and positively charge fluorophores have preference to enter mitochondria [ 86 , 87 ].…”

Photoacid Generators Activated through Sequential Two-Photon Excitation: 1-Sulfonatoxy-2-alkoxyanthraquinone Derivatives

“…Many exciting applications of nr-TPA have been described. [31][32][33][34][35][36] However, one drawback to this method is that the high photon densities required for simultaneous absorption typically require the use of expensive femtosecond lasers and/or high resolution optical set-ups. This in turn increases the expense and limits the ability to run such processes on scale.…”

Recent Advances in Polymeric Nanoparticles for Enhanced Fluorescence and Photoacoustic Imaging

“…Recent developments in the use of two‐photon (TP) fluorogenic probes, [5] as well as probes capable of imaging in the second near‐infrared window (NIR‐II; 1000–1700 nm), [6] have made it possible to image a variety of enzymatic activities directly in human tissues and small animals. For example, a TP small‐molecule probe was recently used to directly report the activity of monoamine oxidase A (MAO‐A), an important enzyme involved in numerous neurodegenerative diseases, in human glioma tissues [7] . An NIR‐II dye, upon successful conjugation to an anti‐EGFR (epidermal growth factor receptor) antibody, was recently reported for the first time for precise image‐guided tumour‐removal surgery with superior targeting properties and a high tumour‐to‐background signal ratio [8] .…”

“…[4] However,a saconsequence of insufficient tissue penetration and background autofluorescence,s uch probes offer only limited applications,m ostly in cell-based imaging.Recent developments in the use of two-photon (TP) fluorogenic probes, [5] as well as probes capable of imaging in the second near-infrared window (NIR-II;1 000-1700 nm), [6] have made it possible to image av ariety of enzymatic activities directly in human tissues and small animals.F or example,aTP small-molecule probe was recently used to directly report the activity of monoamine oxidase A( MAO-A), an important enzyme involved in numerous neurodegenerative diseases,i nh uman glioma tissues. [7] An NIR-II dye, upon successful conjugation to an anti-EGFR (epidermal growth factor receptor) antibody,w as recently reported for the first time for precise image-guided tumour-removal surgery with superior targeting properties and ah igh tumour-to-background signal ratio. [8] Besides fluorescence imaging,i ts hould be noted that luminescence imaging is also ap romising direction for bioimaging as ar esult of its high sensitivity and specificity.…”