Optical Imaging Using SESORRS Reveals Deep-Seated Tumors in Preclinical Cancer Models

In optical imaging, achieving high selectivity and specificity for deep tumor detection remains a major challenge. Surface-enhanced resonant Raman scattering (SERRS) nanoparticles serve as powerful contrast agents for in vivo imaging, offering exceptional molecular sensitivity. However, traditional Raman spectroscopy suffers from limited tissue penetration, typically only a few millimeters, and often requires time-consuming point-by-point acquisition. To overcome these barriers, we integrate spatially offset Raman spectroscopy (SORS) with SERRS in a technique known as surface-enhanced spatially offset resonance Raman spectroscopy (SESORRS). Using SESORRS, we achieve non-invasive detection of deep-seated tumors, confirmed by MRI and H&E staining, and demonstrate its application in colorectal cancer models using tissue phantoms. Importantly, under neutral to basic conditions, pH-responsive hydrolysis of the silica shell triggers dye release and enhances the SERS signal, defining an optimal time window for imaging. This pH-triggered activation enables dynamic monitoring of nanoparticle uptake, intracellular localization, and microenvironmental changes, broadening the applicability of SERS and SESORRS for both in vitro and in vivo imaging.