Spatiotemporal tracking of tumor microenvironment and drug efficacy using embedded SERS nanosensors

Spatiotemporal monitoring of the dynamic extracellular microenvironment provides critical insights into tumor progression and drug metabolism. Conventional approaches typically collect overall metabolic information while ignoring spatial variations, limiting our understanding of the heterogeneous tumor microenvironment upon drug stimulation. To address this challenge, we developed a 3D SERS sensing platform by embedding plasmonic nanosensors into a biocompatible matrix within the tumor microenvironment. This platform enables spatiotemporal monitoring of H₂O₂ concentration and pH value through dynamic SERS mapping. The performance of this embedded sensing system was validated by evaluating the efficacy of a nanomotor-based drug carrier, which features a Janus structure with a platinum-catalyzed motor and doxorubicin-loaded exosomes. By tracking the dynamic spatial variation of the metabolic microenvironment, it was found that the active nanomotor not only extended the range of drug-induced oxidative stress from 45 to 70 μm and increased the concentration of deep-tumor H₂O₂ by 3-fold, but also alleviated deeper tumor acidosis compared to passive drug delivery. Consequently, the embedded SERS platform converts traditional average measurements into spatiotemporal tracking, serving as a promising analytical tool for assessing advanced drug nanocarriers beyond conventional endpoint or bulk assays.