Label-Free Single-Particle Surface-Enhanced Raman Spectroscopy Detection of Phosphatidylserine Externalization on Cell Membranes with Multifunctional Micron-Nano Composite Probes.

Monitoring externalization of phosphatidylserine (PS) and gaining insights into molecular events of cell membrane damage are significant for programmed cell death studies. Herein, by encapsulating zeolitic imidazole frameworks-8 with plasmonic gold nanoparticles to form micron-nano composites and using them as a single-particle surface-enhanced Raman spectroscopy (SERS) substrate, we succeeded in real-time discriminating and monitoring the externalization of PS on cell membranes during electrostimulus-induced apoptosis. The micron-nano composite probe provides rich "hot spots" and robust anchoring capacity for cell membranes, achieving the capture and label-free single-particle SERS detection of the externalized PS. By this method, the dynamic PS externalization process differences between cancerous cells and normal cells were clearly revealed of which the cell membrane damage of cancerous cells was more serious than that of normal cells. This method is versatile and robust for monitoring the externalization of PS and uncovering related cell membrane damage mechanisms. This work also broadens the application of metal-organic framework materials for advanced biomedical applications.