A programmable nanoplatform for inflammatory-state reprogramming in psoriasis treatment.

Abstract

Psoriasis is a chronic, immune-mediated inflammatory skin disease. Although current treatments alleviate symptoms, they primarily focus on inflammation suppression through single-target approaches, which fail to comprehensively address the complex pathological imbalances. To overcome this limitation, we developed a programmable delivery system based on a nanocomposite material composed of Tannic acid (TA), Cerium (Ce), and Luteolin (Lut), integrated into an in situ gelling hydrogel platform (TA-Ce-Lut-Gel), enabling multi-dimensional treatment strategy for psoriasis by precisely modulating oxidative stress, immune responses, and skin microbiota. The TA-Ce-Lut metal-polyphenol nanoparticles, constructed through coordination bonds, exhibited a size of 177.30 ± 0.55 nm and high encapsulation efficiency of 72.89 ± 5.32%. Upon incorporation into the hydrogel, this system provided a localized and sustained drug depot. In an imiquimod-induced mouse model of psoriasis (both ear and back), TA-Ce-Lut-Gel significantly reduced skin inflammation, improved skin thickness, erythema, and scaling, showing superior efficacy compared to traditional anti-inflammatory treatments. This system alleviated ROS levels, regulated macrophage M2 polarization, and reshaped the immune response, while also modulating the TRAF6/NF-κB/STAT3 signaling pathway to significantly inhibit pro-inflammatory cytokine secretion. Additionally, combined with NIR irradiation, TA-Ce-Lut-Gel enhanced transdermal drug delivery and antioxidant activity, further enhancing therapeutic effects and promoting skin microbiota recovery. This study presents an effective platform for localized precise treatment of psoriasis, overcoming the limitations of traditional single-target anti-inflammatory therapies and offering a potential strategy for the treatment of other immune-mediated diseases, with broad clinical application prospects.