Combined photothermal ablation and anti-inflammation using ROS-responsive metal-polyphenol nanoplatform for precision therapy of endometriosis

Background: Endometriosis (EMs) is a prevalent gynecological inflammatory disorder characterized by ectopic endometrial tissue growth and a high-ROS microenvironment. In this study, mesoporous silica (mSiO2) was employed to load the COX2 inhibitor celecoxib (CXB), followed by Fe3+-epigallocatechin gallate (EGCG) self-assembly to form a metal-polyphenol coating. The efficacy and biosafety of the resulting nanoparticles (SC@FEG) combined with photothermal therapy (PTT) were systematically investigated, aiming to achieve precise treatment for EMs. Methods: SC@FEG was characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and UV-visible spectroscopy, and its ROS-responsive release and photothermal performance were examined. In ectopic endometrial stromal cells (eESCs), the effects of SC@FEG combined with near-infrared (NIR) irradiation were assessed via CCK-8, Calcein-AM/PI staining, Transwell assays, and Western blotting. Moreover, an EMs mouse model was established, and lesion-targeted accumulation and heating effects were monitored by infrared thermography. Apoptosis and fibrosis of ectopic lesions were examined by TUNEL and Masson staining, while anti-inflammatory efficacy was evaluated by Western blotting and ELISA. Biosafety was further assessed by hemolysis testing, histology, and serum biochemistry. Results: SC@FEG displayed stable physicochemical properties, efficient ROS-responsive release, and excellent photothermal conversion. In vitro, SC@FEG with NIR irradiation markedly suppressed eESCs’ proliferation, migration, and invasion, while reducing COX2 expression. In vivo, SC@FEG accumulated in lesions, induced local hyperthermia under laser irradiation, inhibited lesion growth, promoted apoptosis, alleviated fibrosis, and markedly reduced systemic inflammation, without systemic toxicity. Conclusions: SC@FEG represents a multifunctional nanoplatform that combines photothermal ablation and anti-inflammatory drug delivery, providing safe and precise therapy for EMs.