Self‐Assembled Dictamni Cortex Nanoparticles Ameliorate Psoriasis by Epigenetic Modulation of HSP90AB1 and Suppression of the Inflammatory Response

作者：Zhengyi Zhang, Wenqian Du, Xiaojiang Zhang, Hongbo Cui, Baochen Cheng, Han Xiao, Ke He, Tingyi Yin, Xinyi Liu, Ningyi Xian, Ziyang Wang, Meng Liu, Dan Han, Jiankang Liu, Yan Zheng, Ya Wang · 发表于：Advanced Science · 年份：2025 · DOI：10.1002/advs.202512422 · 被引用次数：5 · 研究领域：Psoriasis: Treatment and Pathogenesis、Vitamin D Research Studies、S100 Proteins and Annexins

Psoriasis, a chronic immune-mediated dermatological disease with high recurrence rates and limited therapeutic efficacy, requires novel treatment strategies. Dictamni Cortex (BXP), a traditional Chinese medicine (TCM), has demonstrated potential in alleviating psoriasis; however, its clinical application is hampered by poor water solubility and low bioavailability. It is developed infinite coordination polymer nanoparticles (BXP-Fe (III) ICPs, NB), which enhance the aqueous solubility by 95-fold and bioavailability of BXP, exerting therapeutic effect through efficient transdermal delivery. NB significantly suppresses keratinocyte hyperproliferation, inflammation, and oxidative stress in both M5 (a cocktail of cytokines)-treated human epidermal keratinocytes (HEKa) cells and imiquimod (IMQ)-induced psoriatic mice. Nascent proteomics identified heat shock protein 90 alpha family class B member 1 (HSP90AB1) as a key target downregulated by NB. It is further revealed that NB suppresses HSP90AB1 transcription by inhibiting its activator, CCCTC-binding factor (CTCF), and disrupts the HSP90AB1-CDC37 (cell division cycle 37, the co-chaperone) chaperone complex, thereby inactivating the pivotal client proteins STAT3 and Akt. Notably, NB demonstrated superior therapeutic efficacy over the canonical HSP90 inhibitor AUY922. This study highlights NB as a promising topical nanotherapy for psoriasis, integrating TCM with modern nanotechnology to overcome pharmacological limitations. The und...