Cetuximab-induced changes to tumor oral mucosa models probed by stimulated Raman spectromicroscopy

Abstract Spontaneous and stimulated Raman spectromicroscopy is reported to investigate the cetuximab uptake in a head and neck cancer oral mucosa model and to unravel drug induced cellular changes in a label-free approach. Specifically, stimulated Raman spectromicroscopy is sensitive to probe the spatial distribution of cetuximab as well as drug-induced changes in spatial distributions of proteins, lipids, and DNA. The distinct vibrational bands of the CH 3 -stretch of proteins and the CH 2 -stretch of lipids indicate drug-induced cellular modifications, which are retrieved by a linear decomposition algorithm. Topical and systemic drug application pathways were studied, indicating an increased total protein content by a factor of ∼2 and ∼1.5, respectively, compared to an untreated control. Protein and lipid profiles as well as drug distributions were monitored, demonstrating the potential of Raman-based spectromicroscopy for probing changes induced by cetuixmab. Following cetuximab therapy, the relative protein content increases, while the lipid concentration decreases. Accumulation of lipid droplet-like structures near tumor cell membranes with less nucleic acid-like material in treated tumor oral mucosa models was also observed. The results are compared to related spectromicroscopy approaches involving fluorescence labels and label-free photothermal expansion indicating that stimulated Raman spectromicroscopy reveals sensitively biological post-treatment effects, while no reduction in tumor size occurs.