Ion-induced plasmonic microneedle patches for ultrasensitive SERS detection hemoporfin in interstitial fluids

Currently, the "one-size-fits-all" therapeutic window strategy for Hemoporfin-mediated photodynamic therapy of port-wine stains overlooks intralesional heterogeneity and interindividual pharmacokinetic differences. Simultaneously, this strategy lacks real-time feedback and personalized adjustment mechanisms. Therefore, the real-time monitoring of hemoporfin distribution in blood vessel and interstitial fluid is very important for finding the best laser illumination time window depended on personalized characterizes including the height, weight and so on. This study developed an ultra-sensitive sensor by integrating surface-enhanced Raman spectroscopy technology with microneedles (SERS-MNs) for monitoring the distribution dynamics of hemoporfin in blood and interstitial fluid within animal skin. Specifically, calcium ions were employed as an aggregating agent to induce the aggregation of gold/silver nanocage particles on the microneedle surface, thereby forming abundant SERS-enhanced "hot spots". Using this sensor, characteristic Raman fingerprint signals of hemoporfin were successfully obtained for the first time, with a detection limit as low as 50 pg/mL. Furthermore, the SERS-MNs sensor not only quantitatively detected hemoporfin in pig skin but also successfully captured characteristic hemoporfin Raman signals in mouse interstitial fluid, blood, and treated patient blood. This revealed the spatiotemporal distribution mechanism of hemoporfin within the vascular system and interstitial fluid. This advancement will aid in determining the optimal therapeutic window for patients, thereby preventing both overtreatment and undertreatment, ultimately achieve precise therapy characterized by "individualization, visualization, and dynamization".