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Introduction/Objective: Endometriosis is a chronic inflammatory disease with limited therapeutic options and frequent adverse effects. This study aimed to develop and evaluate cerium oxide nanoparticles (nanoceria) as a potential therapeutic strategy for endometriosis, investigating their physicochemical characteristics, biodistribution, radiopharmacokinetics, safety profile, and therapeutic effects in an experimental animal model. Methods: Nanoceria were synthesized using a previously established protocol and characterized by atomic force microscopy (AFM) and in vitro release assays. Female Wistar rats were used for in vivo experiments, including a surgically induced endometriosis model. Nanoceria were radiolabeled with technetium-99m to assess labeling stability, biodistribution, and pharmacokinetics following intraperitoneal administration. Therapeutic efficacy was evaluated through macroscopic and histological analysis of endometriotic lesions. Systemic safety was assessed using plasma biochemical markers. All analyses were conducted in an exploratory pilot design (n = 3 per group). results: Nanoceria exhibited a crystalline fluorite structure with nanoscale dimensions and high surface reactivity. In vitro, treatment with nanoceria reduced reactive oxygen species (ROS) levels, improved cell viability under oxidative stress, and downregulated pro-inflammatory cytokines, including TNF-α and IL-6. In the murine model, nanoceria administration significantly decreased endometriotic lesion size and vascularization compared with controls, alongside a reduction in systemic oxidative and inflammatory markers. Results: AFM analysis revealed nanoceria with a mean diameter of 77.8 nm. The release profile showed a peak concentration at approximately 2 hours and a moderate elimination half-life (~4 hours). Radiolabeling efficiency remained above 98% for 24 hours. Biodistribution studies demonstrated predominant renal elimination and notable accumulation at endometriotic lesion sites. Pharmacokinetic analysis indicated rapid tissue distribution and low intravascular retention (t½ = 3.95 ± 1.09 h). Therapeutic evaluation showed a marked reduction in lesion size and inflammatory infiltrate in nanoceria-treated animals compared to those receiving the free cerium compound. Biochemical analyses indicated lower hepatic and metabolic alterations in the nanoceria groups, suggesting improved systemic safety. discussion: These findings suggest that nanoceria exerts a dual action by both mitigating oxidative stress and modulating inflammatory pathways central to the development and progression of endometriosis. The material’s redox cycling between Ce³⁺/Ce⁴⁺ states confers a unique ability to adapt to the local microenvironment, acting as an antioxidant under oxidative conditions while preserving cellular homeostasis. Compared with conventional treatments, nanoceria offers the advantage of targeting the underlying mechanisms of disease progression rather than only alleviating symptoms. Discussion: The findings indicate that nanoceria exhibit favorable physicochemical and biological properties, including stable radiolabeling, efficient tissue distribution, and selective accumulation in endometriotic lesions. The enhanced therapeutic response and reduced systemic toxicity compared to free cerium suggest that nanoscale formulation improves bioavailability and therapeutic performance. These results support the potential of nanoceria as a nanotechnology-based approach for endometriosis management. Conclusion: Nanoceria demonstrated effective lesion regression, targeted biodistribution, and a favorable safety profile in an experimental endometriosis model. Although exploratory, these results highlight nanoceria as a promising therapeutic candidate and provide a strong rationale for further confirmatory studies with expanded sample sizes and mechanistic evaluation.