PN-CeO2 as a potential therapeutic agent for atopic dermatitis: Antioxidant and anti-inflammatory effects.

Atopic dermatitis (AD) is a common inflammatory skin disorder, and oxidative stress plays a central role in its pathogenesis. Nanoceria, owing to its redox-regulating properties, hold promise as a treatment option for AD. Porous ceria nanorods (PN-CeO2) were synthesized to scavenge reactive oxygen species (ROS). PN-CeO2 was characterized by transmission electron microscopy, nitrogen adsorption/desorption tests, energy dispersive spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. Cytotoxicity was assessed using light microscopy and a Cell Counting Kit-8 assay. ROS-scavenging activity was evaluated in keratinocytes and macrophages using flow cytometry. Inflammatory cytokine regulation was analyzed using RT-qPCR and ELISA. An indirect co-culture system was used to examine the effects of PN-CeO2 on keratinocyte-macrophage interactions. Finally, we tested the therapeutic potential of PN-CeO2 in DNFB and MC903 induced AD mouse model. In vitro, PN-CeO2 decreased ROS and modulated cytokine expression in TNFα-stimulated keratinocytes, LPS-stimulated M1 macrophages, and IL4-stimulated M2 macrophages. Cytokine expression in HaCaT cells was also affected by the conditioned medium from M1 type macrophages incubated with PN-CeO2. PN-CeO2 demonstrated a dose-dependent antioxidative effect, outperforming vitamin C to some extent. In vivo, it alleviated skin lesions; reduced mast cell infiltration; and decreased scratching behavior, serum IgE levels, and spleen indices. Mechanistically, PN-CeO2 decreased the tissue ROS levels and activated Nrf2. It also exhibited excellent biocompatibility. Our findings demonstrated that PN-CeO2 effectively reduced ROS and inflammatory cytokines, offering a promising antioxidative approach for AD treatment.