Mitochondrial-Targeted and Near-Infrared Fluorescence Probe for Bioimaging and Evaluating Monoamine Oxidase A Activity in Hepatic Fibrosis

Abstract

Monoamine oxidase A (MAO-A) is a promising diagnostic marker for cancer, depression, Parkinson’s disease, and liver disease. The fluorescence detection of MAO-A in living animals is of extreme importance for the early diagnosis of related diseases. However, the development of specific and mitochondrial-targeted and near-infrared (NIR) fluorescence MAO-A probes is still inadequate. Here, we designed and synthesized four NIR fluorescence probes containing a dihydroxanthene (DH) skeleton to detect MAO-A in complex biological systems. The specificity of our representative probe DHMP2 displays a 31-fold fluorescence turn-on in vitro, and it can effectively accumulate in the mitochondria and specifically detect the endogenous MAO-A concentrations in PC-3 and SH-SY5Y cell lines. Furthermore, the probe DHMP2 can be used to visualize the endogenous MAO-A activity in zebrafish and tumor-bearing mice. More importantly, it is the first time that the MAO-A activity of hepatic fibrosis tissues is detected through the probe DHMP2. The present study shows that the synthesized DHMP2 might serve as a potential tool for monitoring MAO-A activity in vivo and diagnosing related diseases.

Small-molecule fluorescence-based probes for interrogating major organ diseases

“…25). 36 In DHMP2, a dihydroxanthene (DH) moiety serves as the fluorophore, while a propylamine group acts as the recognition group for MAO-A and a quaternary ammonium salt as the mitochondrial-targeting subunit. DHMP2 could be used to detect changes in MAO-A activity with high selectivity and sensitivity in PBS buffer solution and in living cells.…”

Activity-based NIR fluorescent probes based on the versatile hemicyanine scaffold: design strategy, biomedical applications, and outlook

“…60). 317 Fluorescence response results displayed that only probe DHMP2 enabled high contrast detection of MAO-A with 31-fold fluorescence enhancement. Probe DHMP2 was not responsive toward MAO-B, clearly indicating its high specificity for MAO-A.…”

TME-targeting theranostic agent uses NIR tracking for tumor diagnosis and surgical resection and acts as chemotherapeutic showing enhanced efficiency and minimal toxicity

“…Then, cyclohexanone (6) was treated with PBr3 in the solution of DMF and CHCl3 to afford compound (7). The xanthene skeleton was obtained according to a previous report 29 , where the compound (7) was further treated with 4-methoxy salicylaldehyde to yield intermediate (8). Then, compound (11) was constructed by the compound (9) and (10) via quaternization.…”