State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Changchun, 130012, PR China; The First Hospital of Jilin University, Changchun, 130031, PR China.
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China.
Talanta. 2021 Sep 1;232:122442. doi: 10.1016/j.talanta.2021.122442. Epub 2021 Apr 30.
The anti-tumor effects of metformin hydrochloride (MH), an initial pharmacologic agent for type 2 diabetes, were reexamined by surface-enhanced Raman scattering (SERS) spectroscopy. A SERS immuno-tag fabricated by decorating silver nanoparticles (AgNPs) with a specific antibody was employed to trace the dynamic expression of the tumor metastasis-related N-cadherin. With the MH action, the N-cadherin expression on the cell membranes decreases, proving that MH has a pharmacological effect on prohibiting cancer cell metastasis. Another AgNP-based nucleus targeting nanoprobe was adopted to culture with the MH acted cells, which can help the label-free SERS collection of the cell nuclei to explore the MH influences on intranuclear genes and proteins. By analyzing the intranuclear SERS spectra, the find is that MH has impacts on the transcription and translation of genes, thus regulates the expression of tumor metastasis-related proteins (N-cadherins). This study presents a proof-of-concept for MH as a potential drug for diabetes patients associated with tumors. The developed plasmonic immune analytical platform can be extended to assess other substances of the cell membrane and applicable for the SERS-based screening of membrane receptor-related drugs at the cellular level.
盐酸二甲双胍（MH）是治疗 2 型糖尿病的初始药物，其抗肿瘤作用通过表面增强拉曼散射（SERS）光谱进行了重新研究。使用通过用特异性抗体修饰银纳米颗粒（AgNP）制成的 SERS 免疫标签来追踪肿瘤转移相关 N-钙粘蛋白的动态表达。随着 MH 的作用，细胞膜上的 N-钙粘蛋白表达减少，证明 MH 对抑制癌细胞转移具有药理作用。还采用了另一种基于 AgNP 的核靶向纳米探针与 MH 作用的细胞共培养，这有助于对细胞核进行无标记 SERS 收集，以探索 MH 对核内基因和蛋白质的影响。通过分析核内 SERS 光谱，发现 MH 对基因的转录和翻译有影响，从而调节肿瘤转移相关蛋白（N-钙粘蛋白）的表达。本研究为 MH 作为患有肿瘤的糖尿病患者的潜在药物提供了一个概念验证。所开发的等离子体免疫分析平台可扩展到评估细胞膜的其他物质，并适用于基于 SERS 的细胞水平上的膜受体相关药物的筛选。
