Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology & Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety & International (Hong Kong, Macao and Taiwan) Joint Laboratory on Food Safety and Environmental Analysis, College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, PR China.
Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology & Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety & International (Hong Kong, Macao and Taiwan) Joint Laboratory on Food Safety and Environmental Analysis, College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, PR China; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, 361102, PR China.
Anal Chim Acta. 2024 Apr 22;1299:342422. doi: 10.1016/j.aca.2024.342422. Epub 2024 Feb 27.
Ferroptosis, as a novel form of cell death, is becoming one of the hot topics in cancer treatment research. It differs from necrosis and autophagy in that it involves the accumulation of lipid peroxides and is triggered by iron dependency. Recent studies have suggested that this mechanism may alter the viscosity or structure of lipid droplets (LDs). The relationship between LDs viscosity and ferroptosis remains an active area of research with limited reports at present. Additionally, there is a lack of effective anticancer drugs targeting the ferroptosis pathway to promote ferroptosis in tumour cells. Therefore, the development of tools to detect viscosity changes during ferroptosis and targeted therapeutic strategies is of great significance.
By coupling 1,3-indandione with naphthalimide, including decamethylamine as a LDs recognition group, we designed and synthesized an environmental fluorescent probe that induces intramolecular charge transfer (TICT) effects. Notably, the diffusion and transport of intracellular substances may be affected in highly viscous environments. Under such conditions, intracellular iron ions may accumulate, leading to peroxide production and cellular damage, which can trigger ferroptosis. Therefore, WD-1 achieved excellent in situ bioimaging of LDs targeting and its viscosity during ferroptosis in HeLa cells and zebrafish. Furthermore, it was observed that WD-1 effectively differentiated between malignant and normal cells during this process, highlighting its potential significance in distinguishing cellular states. In addition, we used the antitumour drug paclitaxel to study ferroptosis in cancer cells. These findings not only provide an excellent tool for the development of the ferroptosis response, but also are crucial for understanding the biological properties of LDs during the ferroptosis response.
Based on a powerful tool of fluorescent probe with in vivo bioimaging, we developed WD-1 to track the impact of paclitaxel on the process of ferroptosis in living cells. Therefore, we preliminarily believe that paclitaxel may affect the occurrence of ferroptosis and control apoptosis in cancer cells. These findings not only serve as an exceptional tool for advancing our understanding of the ferroptosis response, but furthermore play a vital role in comprehending the biological characteristics of LDs in relation to ferroptosis.
铁死亡作为一种新型的细胞死亡方式，正在成为癌症治疗研究的热点之一。它与坏死和自噬不同，涉及脂质过氧化物的积累，并由铁依赖性触发。最近的研究表明，这种机制可能会改变脂滴（LDs）的粘度或结构。目前，LDs 粘度与铁死亡之间的关系仍然是一个活跃的研究领域，但报道有限。此外，目前缺乏针对铁死亡途径的有效抗癌药物来促进肿瘤细胞发生铁死亡。因此，开发用于检测铁死亡过程中粘度变化的工具和靶向治疗策略具有重要意义。
通过将 1,3-茚二酮与萘酰亚胺偶联，包括作为 LDs 识别基团的十甲基胺，我们设计并合成了一种环境荧光探针，它诱导分子内电荷转移（TICT）效应。值得注意的是，在高粘度环境中，细胞内物质的扩散和运输可能会受到影响。在这种情况下，细胞内的铁离子可能会积累，导致过氧化物的产生和细胞损伤，从而引发铁死亡。因此，WD-1 能够在 HeLa 细胞和斑马鱼中实现对 LDs 靶向及其铁死亡过程中粘度的优异原位生物成像。此外，在这个过程中，我们观察到 WD-1 能够有效地区分恶性和正常细胞，突出了其在区分细胞状态方面的潜在意义。此外，我们使用抗癌药物紫杉醇来研究癌细胞中的铁死亡。这些发现不仅为铁死亡反应的发展提供了一个极好的工具，而且对于理解铁死亡反应过程中 LDs 的生物学特性也至关重要。
基于具有体内生物成像功能的强大荧光探针工具，我们开发了 WD-1 来跟踪紫杉醇对活细胞中铁死亡过程的影响。因此，我们初步认为紫杉醇可能会影响癌细胞中铁死亡和细胞凋亡的发生。这些发现不仅为我们对铁死亡反应的理解提供了一个极好的工具，而且对于理解铁死亡过程中 LDs 的生物学特性也具有重要意义。
