In Situ Visualization of Epidermal Growth Factor Receptor Nuclear Translocation with Circular Bivalent Aptamer
In Situ Visualization of Epidermal Growth Factor Receptor Nuclear Translocation with Circular Bivalent Aptamer
复制标题
使用圆形二价适体对表皮生长因子受体核转位进行原位可视化
DOI：
10.1021/acs.analchem.2c02762
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发表时间：
2022-12-05
影响因子：
7.4
通讯作者：
Yuan，Quan
中科院分区：
文献类型：
--
作者：
Zhang，Lei;Chu，Mengge;Yuan，Quan
表皮生长因子受体（EGFR）核转位与肿瘤细胞的异常增殖、迁移和抗凋亡相关。监测EGFR核转位提供了对癌症潜在分子机制的深入了解。EGFR核转位包括EGFR磷酸化和磷酸化EGFR核转位两个过程。在适体的帮助下，已经开发出可以实现锚定磷酸化EGFR的第一步的探针。然而，EGFR核转位可以持续数小时，这对监测活细胞中的整个核转位构成了挑战。在此，我们设计了一种环状二价适体功能化的光学探针，其具有大大增强的稳定性，用于EGFR核易位原位的长期可视化。细胞实验结果表明，该探针可监测EGFR的全核转位。组织和体内实验结果表明，该探针可以通过原位成像EGFR核转位来评估肿瘤的发生和发展。该方法可以长期监测EGFR核转位，表明其在研究癌症机制和指导肿瘤治疗方面具有巨大潜力。
Epidermal growth factor receptor (EGFR) nuclear translocation correlates with the abnormal proliferation, migration, and anti-apoptosis of tumor cells. Monitoring EGFR nuclear translocation provides insights into the molecular mechanisms underlying cancers. EGFR nuclear translocation includes two processes, EGFR phosphorylation and phosphorylated EGFR translocation to the nucleus. With the help of aptamers, probes that can achieve the first step of anchoring phosphorylated EGFR have been developed. However, the EGFR nuclear translocation can last for hours, posing a challenge to monitor the entire nuclear translocation in living cells. Herein, we designed a circular bivalent aptamer-functionalized optical probe with greatly enhanced stability for long-term visualization of EGFR nuclear translocation in situ. The results of cell experiments show that the probe could monitor the entire nuclear translocation of EGFR. The findings of tissue andin vivoexperiments demonstrate that the probe can evaluate the development and progression of tumors by imaging EGFR nuclear translocation in situ. The proposed approach allows us to monitor EGFR nuclear translocation in the long term, indicating its great potential in investigating the mechanisms of cancers and guiding for tumor treatment.