Department of Medicinal Chemistry, College of Pharmacy, UF Health Science Center, University of Florida, Gainesville, Florida 32610, United States.
Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131, United States.
J Med Chem. 2021 Dec 23;64(24):17969-17978. doi: 10.1021/acs.jmedchem.1c01313. Epub 2021 Nov 9.
Cellular senescence, a process that arrests the cell cycle, is a cellular response mechanism for various stresses and is implicated in aging and various age-related diseases. However, the understanding of senescence in living organisms is insufficient, largely due to the scarcity of sensitive tools for the detection of cellular senescence . Herein, we describe the development of a self-immobilizing near-infrared (NIR) fluorogenic probe that can be activated by senescence-associated βgalactosidase (SA-βGal), the most widely used senescence marker. The NIR signal is turned on only in the presence of SA-βGal, and the fluorescence signal is retained to the site of activation labeling, significantly enhancing the sensitivity of the probe. We demonstrate its efficient noninvasive imaging of senescence in mice xenograft models.
细胞衰老，一种阻止细胞周期的过程，是细胞对各种应激的反应机制，与衰老和各种与年龄相关的疾病有关。然而，对生物体中衰老的理解还不够充分，这主要是因为缺乏用于检测细胞衰老的敏感工具。在此，我们描述了一种自固定近红外（NIR）荧光探针的开发，该探针可以被衰老相关β半乳糖苷酶（SA-βGal）激活，SA-βGal 是最广泛使用的衰老标志物之一。只有在存在 SA-βGal 的情况下，NIR 信号才会被激活，并且荧光信号保留在激活部位，从而显著提高了探针的灵敏度。我们证明了它在小鼠异种移植模型中对衰老进行高效的非侵入性成像的能力。
