Nanoceria as a non-steroidal anti-inflammatory drug for endometriosis theranostics.

Endometriosis, the growth of endometrial-like tissue outside the uterus, causes chronic pain and infertility in 10 % of reproductive-aged women worldwide. Unfortunately, no permanent cure exists, and current medical and surgical treatments offer only temporary relief. Endometriosis is a chronic inflammatory disease characterized by immune system dysfunction. Our previous study showed aberrant activation of signal transducer and activator of transcription 3 (STAT3) in endometriosis. Our transcriptomic analysis of uterine tissue from uterine-specific Stat3 knock-out mice identifies that STAT3 regulates inflammatory and immune-related genes. Here, we evaluate cerium-oxide nanoparticles (nanoceria) as a non-steroidal anti-inflammatory drug for endometriosis theranostics. Our in vitro studies validate the multi-enzymatic properties of nanoceria, enabling the transition of pro-inflammatory macrophages to an anti-inflammatory state in J774 macrophage cells. In vivo, treatment of endometriosis mice with nanoceria reveals its ability to passively accumulate at ectopic lesions. The nanoceria conjugated with indocyanine green are non-invasively trackable to ectopic lesions. Therefore, immune modulation and anti-inflammatory effects of nanoceria significantly reduce development of ectopic lesions while minimizing off-target effects, such as avoiding interference with pregnancy including implantation and decidualization. Our results suggest that aberrant STAT3 activation is a major contributor to endometriosis, and nanoceria offers a novel theranostic approach for endometriosis.