An Intelligent Hyperthermia System with Photothermal Temperature Wall Effect for Programmable Gated Drug Release in Wound Healing

Abstract Traditional photothermal therapy (PTT) inevitably causes thermal damage and uncontrolled drug release (DR) owing to the continuous increase and fluctuation in the photothermal temperature. Herein, a photothermal temperature wall (PTW)‐gated drug‐release system is developed for use in the safe PTT of wounds. This system is implemented via two modules integrated within a hydrogel: i) photothermal color‐changing (PCC) microcapsules with PTW effects, and ii) temperature‐sensitive drug‐loaded microspheres for gradient PTW‐programed DR. The PTW effect is realized via the dynamic “on‐off” dual‐modal switching of the photothermal properties, and it can be regulated by adjusting the molecular chain lengths of the saturated fatty alcohols and near‐infrared power density employed. The drug‐release threshold of temperature‐sensitive microspheres can also be tailored by varying the mass ratio of N‐isopropylacrylamide‐co‐N‐hydroxymethylacrylamide (shell) to gelatin‐co‐agarose (core). Consequently, the personalized programed release of thrombin, vancomycin, and basic fibroblast growth factor (bFGF) to address the respective drug requirements during the hemostasis, inflammation, and proliferation stages of infected mouse wounds, is realized. This leads to a highly efficient wound healing rate (99.9%) within 15 days. Therefore, this system holds promise as a viable candidate for use in personalized drug delivery during wound treatment.