Metformin Hydrochloride Action on Cell Membrane N-cadherin Expression and Cell Nucleus Revealed by SERS Nanoprobes

ABSTRACT 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 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.