H2S激活型荧光探针,能够在肿瘤细胞中实现双通道荧光追踪药物释放。
H2S-activated fluorescent probe enables dual-channel fluorescence tracking of drug release in tumor cells.
发表日期:2023 Mar 29
作者:
Caiyun Liu, Yan Zhang, Weimin Sun, Hanchuang Zhu, Meijun Su, Xin Wang, Xiaodi Rong, Kun Wang, Miaohui Yu, Wenlong Sheng, Baocun Zhu
来源:
BIOORGANIC CHEMISTRY
摘要:
现今,由于化疗药物副作用严重,将治疗药物有选择地释放到肿瘤细胞内已成为肿瘤治疗的重要方式。氢硫化物(H2S)作为气体介质之一与癌症密切相关。由于肿瘤细胞内H2S含量高,它可以被用作信号分子来触发药物释放,从而实现治疗药物的选择性释放。此外,双通道荧光成像技术可以更好地用于监测药物输送过程并区分药物释放前后的状态,从而更好地跟踪药物治疗的效果。基于此,我们使用NBD胺(NBD-NHR)作为H2S的识别基团,并连接酪氨酸激酶抑制剂克唑替尼以构建激活的双通道荧光探针CZ-NBD。当探针进入肿瘤细胞后,它会消耗H2S并释放对肿瘤细胞具有高毒性的克唑替尼。重要的是,探针在不同细胞中显示出显著的荧光变化,不仅可以筛选肿瘤细胞,还可以追踪和监测药物释放和肿瘤细胞活动。因此,探针CZ-NBD的构建为肿瘤细胞中药物释放监测提供了一种新的策略。Copyright © 2023 Elsevier Inc. All rights reserved.
Nowadays, the selective release of therapeutic drugs into tumor cells has become an important way of tumor treatment due to the high side effects of chemotherapy drugs. As one of the gas mediators, hydrogen sulfide (H2S) is closely related to cancer. Due to the high content of H2S in tumor cells, it can be used as a signaling molecule that triggers the release of drugs to achieve the selective release of therapeutic drugs. In addition, dual-channel fluorescence imaging technology can be better applied to monitor the drug delivery process and distinguish the state before and after drug release, so as to better track the effect of drug therapy. Based on this, we used NBD amines (NBD-NHR) as the recognition group of H2S and connected the tyrosine kinase inhibitor crizotinib to construct an activated dual-channel fluorescent probe CZ-NBD. After the probe enters the tumor cells, it consumes H2S and releases crizotinib, which is highly toxic to the tumor cells. Importantly, the probe displays significant fluorescence changes in different cells, enabling not only the screening of tumor cells, but also tracking and monitoring drug release and tumor cell activity. Therefore, the construction of probe CZ-NBD provides a new strategy for drug release monitoring in tumor cells.Copyright © 2023 Elsevier Inc. All rights reserved.