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

Abstract

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.