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Here we show that the cyclic GMP\u2010AMP synthase (cGAS)\u2010stimulator of interferon genes (STING) pathway is a key regulator of psoriatic inflammation in a mouse model. Platinum\u2010doped positively charged carbon dots (Pt\u2010CDs) were designed to inhibit the cGAS\u2010STING pathway. By inhibiting the cGAS\u2010STING pathway with Pt\u2010CDs, the secretion of proinflammatory cytokines in macrophages was reduced, and the proinflammatory cytokines\u2010induced breakdown of immunological tolerance and overexpression of chemokines in keratinocytes was restored, which reversed the homeostatic imbalance through breaking these cytokines\u2010mediated intercellular positive feedback loop. Topical Pt\u2010CDs treatment exhibited therapeutic effects in imiquimod\u2010induced psoriasis mice without noticeable toxicity. The reversal of elevated expression of STING, phosphorylated STING, and downstream genes within psoriatic lesions indicates that Pt\u2010CDs effectively inhibit the cGAS\u2010STING pathway. This work suggests a promising strategy for psoriasis treatment by targeting the cGAS\u2010STING pathway with Pt\u2010CDs nanoinhibitor to restore skin homeostatic balance.<\/jats:p>","DOI":"10.1002\/anie.202316007","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T23:10:19Z","timestamp":1701213019000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["A Nanoinhibitor Targeting cGAS\u2010STING Pathway to Reverse the Homeostatic Imbalance of Inflammation in Psoriasis"],"prefix":"10.1002","volume":"63","author":[{"given":"Zhibin","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Engineering and Applied Sciences Jiangsu Key Laboratory of Artificial Functional Materials State Key Laboratory of Analytical Chemistry for Life Science Collaborative Innovation Center of Advanced Microstructures Nanjing University  Nanjing 210093 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