Removable SERS Microneedles with In Situ Thermal Feedback for Precise Photothermal Therapy of Infected Wounds

Abstract The lack of precise thermal feedback from local treatment sites and potential safety risks caused by the shedding of sensing materials remain critical bottlenecks, limiting the clinical translation of in vivo implantable sensors and therapeutic platforms. Herein, we report removable, near-infrared (NIR)-responsive surface-enhanced Raman scattering (SERS) microneedles with actual subcutaneous temperature feedback (RTF-SEMNs). Constructed on rigid polymethyl methacrylate (PMMA) arrays, the microneedle tips are densely modified with gold nanoparticles (AuNPs). For in situ thermal monitoring, a highly robust ratiometric SERS strategy is employed, using a stable internal standard combined with a NIR-responsive thermal reporter (3,3′-diethylthiatricarbocyanine iodide, DTTC). The entire platform is encapsulated within a porous polystyrene−polyethylene glycol (PS-PEG) layer, enabling subsequent postloading of DTTC molecules through the nanoporous structure. This unique structural design physically immobilizes AuNPs to minimize nanoparticle leakage, while fully retaining the inherent NIR responsiveness of the reporter. The platform demonstrates favorable preliminary biosafety in local tissues, as evidenced by rapid puncture closure within 30 min and extremely low residual gold levels in tissue after removal (0.34 pg/g). As a proof of concept, this implantable SERS thermometer enables precise guidance of photothermal therapy (PTT) for Staphylococcus aureus-infected wounds. It provides in situ readout of the actual subcutaneous treatment-site temperature (∼49.6 °C), in contrast to conventional NIR thermography, which only regulates treatment based on superficial skin temperature (∼50.3 °C). With accurate subcutaneous thermal feedback, the platform achieves improved antibacterial therapeutic outcomes and clearly accelerates epidermal regeneration by day 11 posttreatment. This work establishes a minimally invasive, low-residue platform for treatment-site-temperature-guided PTT and offers a promising strategy toward safer and more precise in vivo therapeutic monitoring and intervention.