Cellular senescence imaging and senolysis monitoring in cancer therapy based on a β-galactosidase-activated aggregation-induced emission luminogen,Acta Biomaterialia

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Cellular senescence imaging and senolysis monitoring in cancer therapy based on a β-galactosidase-activated aggregation-induced emission luminogen
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2024-03-30 , DOI: 10.1016/j.actbio.2024.03.027
Peili Cen ₁ , Chunyi Cui ₁ , Jiani Huang ₁ , Hetian Chen ₁ , Fei Wu ₁ , Jiaqi Niu ₁ , Yan Zhong ₁ , Chentao Jin ₁ , Wei-Hong Zhu ₂ , Hong Zhang ₃ , Mei Tian ₄

Affiliation

Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, Zhejiang 310009, China; Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, Zhejiang 310009, China.
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China.
Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, Zhejiang 310009, China; Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, Zhejiang 310009, China; College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310014, China; Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310014, China.
Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, Zhejiang 310009, China; Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, Zhejiang 310009, China; Human Phenome Institute, Fudan University, Shanghai 201203, China.

Cellular senescence is a permanent state of cell cycle arrest characterized by increased activity of senescence associated β-galactosidase (SA-β-gal). Notably, cancer cells have been also observed to exhibit the senescence response and are being considered for sequential treatment with pro-senescence therapy followed by senolytic therapy. However, there is currently no effective agent targeting β-galactosidase (β-Gal) for imaging cellular senescence and monitoring senolysis in cancer therapy. Aggregation-induced emission luminogen (AIEgen) demonstrates strong fluorescence, good photostability, and biocompatibility, making it a potential candidate for imaging cellular senescence and monitoring senolysis in cancer therapy when endowed with β-Gal-responsive capabilities. In this study, we introduced a β-Gal-activated AIEgen named QM-β-gal for cellular senescence imaging and senolysis monitoring in cancer therapy. QM-β-gal exhibited good amphiphilic properties and formed aggregates that emitted a fluorescence signal upon β-Gal activation. It showed high specificity towards the activity of β-Gal in lysosomes and successfully visualized DOX-induced senescent cancer cells with intense fluorescence both and . Encouragingly, QM-β-gal could image senescent cancer cells for over 14 days with excellent biocompatibility. Moreover, it allowed for the monitoring of senescent cancer cell clearance during senolytic therapy with ABT263. This investigation indicated the potential of the β-Gal-activated AIEgen, QM-β-gal, as an approach for imaging cellular senescence and monitoring senolysis in cancer therapy via highly specific and long-term fluorescence imaging. This work reported a β-galactosidase-activated AIEgen called QM-β-gal, which effectively imaged DOX-induced senescent cancer cells both and . QM-β-gal specifically targeted the increased expression and activity of β-galactosidase in senescent cancer cells, localized within lysosomes. It was cleared rapidly before activation but maintained stability after activation in the DOX-induced senescent tumor. The AIEgen exhibited a remarkable long-term imaging capability for senescent cancer cells, lasting over 14 days and enabled monitoring of senescent cancer cell clearance through ABT263-induced apoptosis. This approach held promise for researchers seeking to achieve prolonged imaging of senescent cells .

中文翻译：

基于β-半乳糖苷酶激活聚集诱导发射发光体的癌症治疗中的细胞衰老成像和衰老作用监测

细胞衰老是细胞周期停滞的永久状态，其特征是衰老相关 β-半乳糖苷酶 (SA-β-gal) 活性增加。值得注意的是，癌细胞也被发现表现出衰老反应，并正在考虑采用促衰老疗法和抗衰老疗法进行序贯治疗。然而，目前尚无有效的靶向β-半乳糖苷酶（β-Gal）的药物用于对细胞衰老进行成像并监测癌症治疗中的衰老作用。聚集诱导发射发光原 (AIEgen) 表现出强荧光、良好的光稳定性和生物相容性，当其具有 β-Gal 响应能力时，使其成为细胞衰老成像和癌症治疗中衰老作用监测的潜在候选者。在这项研究中，我们引入了一种名为 QM-β-gal 的 β-Gal 激活的 AIEgen，用于癌症治疗中的细胞衰老成像和衰老作用监测。 QM-β-gal 表现出良好的两亲特性，并形成聚集体，在 β-Gal 激活时发出荧光信号。它对溶酶体中 β-Gal 的活性表现出高度特异性，并成功地将 DOX 诱导的衰老癌细胞可视化，并具有强烈的荧光。令人鼓舞的是，QM-β-gal 可以对衰老癌细胞进行超过 14 天的成像，并且具有出色的生物相容性。此外，它还可以在 ABT263 的 senolytic 治疗期间监测衰老癌细胞的清除情况。这项研究表明了 β-Gal 激活的 AIEgen（QM-β-gal）作为一种通过高度特异性和长期荧光成像对细胞衰老进行成像并监测癌症治疗中衰老作用的方法的潜力。这项工作报道了一种名为 QM-β-gal 的 β-半乳糖苷酶激活的 AIEgen，它可以有效地对 DOX 诱导的衰老癌细胞进行成像。 QM-β-gal 专门针对位于溶酶体内的衰老癌细胞中 β-半乳糖苷酶的表达和活性增加。在 DOX 诱导的衰老肿瘤中，它在激活前被迅速清除，但在激活后保持稳定。 AIEgen 对衰老癌细胞表现出卓越的长期成像能力，持续超过 14 天，并能够通过 ABT263 诱导的细胞凋亡监测衰老癌细胞的清除情况。这种方法为寻求对衰老细胞进行长时间成像的研究人员带来了希望。

更新日期：2024-03-30

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