Aptamer Conjugate-Based Ratiometric Fluorescent Probe for Precise Imaging of Therapy-Induced Cancer Senescence

Therapy-induced cellular senescence has been increasingly recognized as a key mechanism to promote various aspects of carcinogenesis in a nonautonomous manner. Thus, real-time imaging monitoring of cellular senescence during cancer therapy is imperative not only to further elucidate its roles in can...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2024-01, Vol.96 (1), p.154-162
Main Authors: Wang, Linlin, Li, Jili, Zhao, Zhihui, Xia, Yinghao, Xie, Yuqi, Hong, Donghui, Liu, Yanlan, Tan, Weihong
Format: Article
Language:English
Subjects:
Aptamers
Cancer
Cancer therapies
Carcinogenesis
Carcinogens
Conjugates
Cyanine dyes
Fluorescence
Fluorescent indicators
Medical imaging
Multicellular tumor spheroids
Senescence
Spheroids
Therapy
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Summary:Therapy-induced cellular senescence has been increasingly recognized as a key mechanism to promote various aspects of carcinogenesis in a nonautonomous manner. Thus, real-time imaging monitoring of cellular senescence during cancer therapy is imperative not only to further elucidate its roles in cancer progression but also to provide guidance for medical management of cancer. However, it has long been a challenging task due to the lack of effective imaging molecule tools with high specificity and accuracy toward cancer senescence. Herein, we report the rational design, synthesis, and evaluation of an aptamer conjugate-based ratiometric fluorescent probe for precise imaging of therapy-induced cancer senescence. Unlike traditional senescence imaging systems, our probe targets two senescence-associated markers at both cellular and subcellular dimensions, namely, aptamer-mediated membrane marker recognition for active cell targeting and lysosomal marker-triggered ratiometric fluorescence changes of two cyanine dyes for site-specific, high-contrast imaging. Moreover, such a two-channel fluorescence response is activated after a one-step reaction and at the same location, avoiding the diffusion-caused signal decay previously encountered in dual-marker activated probes, contributing to spatiotemporally specific imaging of therapy-induced cancer senescence in living cells and three-dimensional multicellular tumor spheroids. This work may offer a valuable tool for a basic understanding of cellular senescence in cancer biology and interventions.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.3c03435