Surface-Enhanced Raman Scattering Imaging of Dynamic pH Changes in Lysosomes during Cancer Cell Invasion on a Microfluidic Chip

Lysosomes are important organelles involved in intracellular degradation and nutrition-dependent signal transduction. While existing studies have primarily focused on lysosomal pH changes during processes such as lysosomal membrane damage leading to cell death, investigations into lysosomal pH alterations during cell invasion have been largely overlooked. Here, we present a method to analyze lysosomal pH changes during cancer cell invasion using a microfluidic chip-based surface-enhanced Raman scattering (SERS) technique for real-time imaging. Our custom-designed microfluidic chip simulated the cell invasion process, enabling simultaneous, real-time, and in situ SERS monitoring of cells exhibiting varying degrees of invasion and migration. The synthesized pH nanoprobe is based on 4-MPy-modified gold-silver core-shell nanoparticles, boasting good biocompatibility, a high SERS enhancement effect, and subcellular-level targeted monitoring capabilities. Through our SERS microfluidic chip, we observed a slight decrease in lysosomal pH and a slight increase in extracellular pH, with lysosomes predominantly located in the cell periphery during cell invasion. This study contributes to a deeper understanding of the relationship between lysosomes and cancer metastasis.