Compensatory effect-based oxidative stress management microneedle for psoriasis treatment

Reactive oxygen species (ROS) at elevated levels trigger oxidative DNA damage, which is a significant factor in psoriasis exacerbation. However, normal ROS levels are essential for cell signaling, cell growth regulation, differentiation, and immune responses. To address this, we developed ROS control strategies inspired by compensatory effects. DNA nanostructures with the advantage of being more stable than linear nucleic acid molecules in physiological environments were exquisitely fabricated and incorporated into microneedles (MN). These nanostructures regulate ROS levels and facilitate the delivery of IL-17A siRNA to psoriatic lesions. Our findings demonstrate that this transdermal drug delivery system effectively manages ROS levels in the psoriatic microenvironment, inhibiting pyroptosis and abnormal immune activation. Moreover, modulating ROS levels enhances the therapeutic impact of IL-17A siRNA, offering a promising in situ treatment approach for psoriasis. Psoriasis, marked by red, scaly patches, is exacerbated by high ROS levels, yet ROS are vital for cellular functions. A novel DNA nanostructure-loaded microneedle system balances ROS, inhibits pyroptosis, and enhances IL-17A siRNA therapy for psoriasis, presenting a promising targeted treatment. This approach advances psoriasis research by addressing ROS-mediated pathogenesis. • The DNA nanostructure complex modulated inflammatory microenvironment and amplified the efficacy of siRNA delivery. • The siRNA downregulated the psoriasis target IL-17A. • Microneedles increased the drug delivery efficiency and maintain time. • The microneedle patch modulated the psoriasis immunity microenvironment and treated psoriasis.