Redox-Responsive Surface-Enhanced Raman Scattering Microneedles for Monitoring Acupuncture Responses in Rats With...

Impaired glucose tolerance (IGT) is associated with disturbed redox homeostasis and increased oxidative stress, but dynamic in vivo tracking of redox-associated changes during acupuncture intervention remains technically challenging. This study developed a redox-sensitive surface-enhanced Raman scattering (SERS)-active microneedle system for simultaneous acupuncture intervention and relative ratiometric tracking of oxidative capacity (OC)- and redox potential (RP)-related SERS indices in rats with IGT. Oxidative- and redox-sensitive SERS probes were prepared by functionalizing gold nanoshells (GNS) with p-phenylenediamine (p-PDA) for OC responsiveness and anthraquinone for RP responsiveness, respectively. The probes were loaded into two etched grooves on acupuncture needles to construct SERS-active microneedles. Specific-pathogen-free male Sprague-Dawley rats were used in this exploratory study. Three rats served as normal controls, and 20 rats were fed a high-fat diet and administered streptozotocin (STZ) to induce IGT. After screening, 18 eligible IGT rats were divided into high-fat-diet and normal-diet groups, with 9 rats per diet group. Each diet group was further divided into acupuncture-point twisting, non-acupuncture-site twisting, and acupuncture-point direct-insertion subgroups, with 3 rats per subgroup. Needling was performed twice daily for 7 consecutive days, and fasting blood glucose (FPG), 2 h postprandial blood glucose (2hPG), and OC- and RP-related SERS indices were recorded. The results showed that needling at acupuncture points with twisting was associated with lower FPG and 2hPG values and altered OC- and RP-related SERS indices in this IGT rat model. Because external calibration curves, independent biochemical oxidative-stress assays, probe-leaching tests, and biocompatibility assays were not included, the SERS ratios should be interpreted as relative redox-associated optical indices rather than absolute biochemical concentrations or absolute redox-potential values. These findings support the feasibility of SERS-active microneedles as an exploratory preclinical platform for combining acupuncture intervention with local ratiometric SERS tracking in IGT rats.