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Permeability-Controlled Probe for Ratiometric Detection of Plasma Membrane Integrity and Late Apoptosis
ACS Sensors ( IF 8.2 ) Pub Date : 2024-10-26 , DOI: 10.1021/acssensors.4c01963
Fengkai Sun, Baoli Dong, Heng Zhang, Minggang Tian

The destruction of plasma membrane integrity is closely related to immune response, neuronal injury, cell apoptosis, and other pathological events. However, the construction of ratiometric fluorescent probes capable of detecting plasma membrane integrity remains a significant challenge, hindering in-depth studies on related biomedical areas. Herein, a polarity-responsive fluorescent probe was constructed for the ratiometric detection of cell membrane integrity for the first time. The probe targeted intact plasma membranes in healthy cells and relocated into the cytoplasm to give significantly red-shifted fluorescence after plasma membrane damage. Molecular simulations revealed that the high transmembrane barrier and amphipathic nature of the probe were responsible for its targeting ability. With the probe, the ratiometric detection of late apoptosis stage was realized for the first time, and the membrane damage of tumor cells induced by UV irradiation, toxins, and antitumor drugs was visualized. The effect of formaldehyde on membrane integrity was evaluated using a probe, and cysteine was proved to be a potential detoxifier to counteract the toxicity of formaldehyde.

中文翻译:


用于质膜完整性和晚期细胞凋亡的比率检测的通透性对照探针



质膜完整性的破坏与免疫应答、神经元损伤、细胞凋亡和其他病理事件密切相关。然而,能够检测质膜完整性的比率荧光探针的构建仍然是一个重大挑战,阻碍了对相关生物医学领域的深入研究。在此,首次构建了一种极性响应性荧光探针,用于细胞膜完整性的比例检测。探针靶向健康细胞中的完整质膜,并重新定位到细胞质中,在质膜损伤后产生显著的红移荧光。分子模拟显示,探针的高跨膜屏障和两亲性是其靶向能力的原因。利用探针,首次实现了晚期细胞凋亡阶段的比率检测,可视化了紫外线照射、毒素和抗肿瘤药物诱导的肿瘤细胞膜损伤。使用探针评估甲醛对膜完整性的影响,半胱氨酸被证明是抵消甲醛毒性的潜在解毒剂。
更新日期:2024-10-26
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