Double-stranded RNA and ROS scavenging nanoplatform for modulating skin inflammation

Double-stranded RNA (dsRNA) and reactive oxygen species (ROS) contribute to the exacerbation of skin inflammatory diseases such as psoriasis and atopic dermatitis. While antioxidant strategies have been extensively explored, approaches to neutralize pathogenic dsRNA remain limited. Here, we show that Mo90Ce10, a cerium-doped polyoxometalate, concurrently targets dsRNA and ROS to mitigate cutaneous inflammation. In vitro, Mo90Ce10 scavenges ROS and suppresses type I interferon responses by directly binding dsRNA through its oxygen-rich, hydrogen bond-forming surface. Its structural template, {Mo154}, exhibits weaker activity. In vivo, Mo90Ce10 reduces disease severity, dsRNA-induced inflammation, ROS burden, and neutrophil infiltration. Leveraging its negative charge and self-assembly properties, we further develop a transdermal platform by complexing Mo90Ce10 with the cationic peptide TD-1 and co-loading methotrexate, thereby enhancing drug penetration andtherapeutic efficacy while reducing recurrence. Together, these findings establish Mo90Ce10 as a multifunctional modulator of dsRNA- and ROS-driven inflammation and a promising transdermal delivery platform for inflammatory diseases. Oxidative stress and dsRNA are key drivers of skin inflammation, while therapies targeting oxidative stress are common, dsRNA targeting is not. Here, the authors report on a cerium-doped polyoxometalate with anti-oxidative and dsRNA binding properties showing potential for a transdermal strategy to reduce skin inflammation.