用于体内极性感应和癌症治疗的溶酶体特异性香豆素类荧光生物探针。
Lysosome-Specific Coumarin-Based Fluorescent Bioprobes for in Vivo Polarity Sensing and Cancer Treatment.
发表日期:2023 Sep 14
作者:
Xian Chen, Wenjing Wang, Tangying Ye, Jialu Kang, Qianqiu Wang, Wei Yang, Heshuang Dai, Kai Wang, Jie Pan
来源:
Cell Death & Disease
摘要:
全球约90%的癌症死亡由癌细胞从原发肿瘤转移到远处器官(转移)引起。因此,在癌症转移发生之前,急需早期诊断和治疗。溶酶体已成为癌症诊断和治疗的吸引人靶标,因为溶酶体的极性缺陷可以诱导凋亡和细胞死亡。库马林是一种已知具有良好生物相容性的极性敏感染料;因此,我们通过三个简单的反应构建了两个库马林衍生物的荧光探针,CouN-1和CouN-2,在“D-π-A”结构中。在分子设计上,由于吗啉具有突出的溶酶体靶向特性,将其作为溶酶体靶向基团和电子供体(D)使用,库马林则用作电子受体(A)。实验结果强烈证明了CouN-1和CouN-2与极性变化之间具有良好的线性关系,Δf = 0.209-0.308。此外,无论是体外还是体内成像结果都显示CouN-1和CouN-2可以特异性地识别和监测肿瘤部位。在细胞摄取和凋亡实验中,这两个探针在抗癌细胞增殖方面也表现出强烈的效果。所有这些特性展示了这两种极性敏感的生物探针CouN-1和CouN-2在癌症诊断和治疗方面的潜力。
About 90% of cancer deaths worldwide are caused by the spread of cancer cells from the primary tumor to distant organs (metastasis). Therefore, there is an urgent need for an early diagnosis and treatment before cancer metastasis occurs. Lysosomes have emerged as attractive targets for cancer diagnosis and treatment because polar defects in lysosomes can induce apoptosis and cell death. Coumarin is a known polar-sensitive dye with good biocompatibility; because of this, we constructed two fluorescent probes of coumarin derivatives with the "D-π-A" structure, CouN-1 and CouN-2, through three simple reactions. In molecular design, due to morpholine's prominent lysosomal targeting characteristics, it was used as both lysosomal targeting motifs and an electron donor (D), while coumarin was used as an electron acceptor (A). The experimental results strongly proved that CouN-1 and CouN-2 have a good linear relationship with the polarity change of Δf = 0.209-0.308. In addition, both in vitro and in vivo imaging results have shown that CouN-1 and CouN-2 can specifically identify and monitor tumor sites. In the cell uptake and apoptosis experiments, the two probes also showed a strong antiproliferation effect on cancer cells. All of these characteristics demonstrated the potential of these two polarity-sensitive biological probes, CouN-1 and CouN-2, in the diagnosis and treatment of cancer.