Ultrasound-Assisted Cerium-Doped Zeolite Nanocomplex Attenuates Adenomyosis via Wnt/beta-Catenin Pathway Inhibition and IGFBP5 Downregulation in SFRP4+ NKT Cells

Adenomyosis is a chronic gynecological disorder characterized by ectopic endometrial tissue within the myometrium, leading to pelvic pain, menorrhagia, and infertility. Increasing evidence implicates dysregulated Wnt/beta-catenin signaling and aberrant activation of SFRP4+ natural killer T (NKT) cells in disease progression. This study reports the ultrasound-assisted synthesis of a cerium-doped zeolite nanocomplex (Ce-ZNC) and evaluates its therapeutic efficacy in experimental models of adenomyosis. Ce-ZNC was synthesized via an ultrasound-assisted doping approach and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and polydispersity index (PDI) analysis. In vitro studies were conducted on human peripheral blood mononuclear cell (PBMC)-derived SFRP4+ NKT cells. In vivo efficacy was evaluated in a murine adenomyosis model. IGFBP5 expression and Wnt/beta catenin signaling components were analyzed by RT-qPCR and Western blotting. Histological and cytokine analyses were performed to assess fibrosis and inflammation. Ce-ZNC exhibited spherical morphology with nanoscale dimensions and good colloidal stability. Treatment resulted in a dose-dependent suppression of IGFBP5 expression and inhibition of Wnt/beta-catenin signaling. In vivo administration significantly reduced uterine fibrosis, glandular invasion, and inflammatory cytokine levels. These findings suggest that Ce-ZNC exerts immunomodulatory and anti-fibrotic effects in adenomyosis. While promising, further studies are required to elucidate biodistribution, long-term safety, and translational potential in human models. Key words Adenomyosis " Cerium-doped zeolite " Nanomedicine " Wnt/beta-catenin pathway " IGFBP5 " SFRP4+ NKT cells " Inflammation " Fibrosis " Ultrasound-assisted synthesis.