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Here, cell membrane\u2010coated nanoparticles (CNPs) are designed to simultaneously inhibit T cell activation and KC hyperproliferation for optimized psoriasis therapy. A customized cell membrane is genetically engineered to overexpress the immunoregulatory V\u2010domain immunoglobulin suppressor of T cell activation (VISTA) protein to enable potent T\u2010cell inhibition. The encapsulated core is designed as Janus nanoparticles (mSiO\n                    <jats:sub>2<\/jats:sub>\n                    &amp;rPMO) for co\u2010delivery of hydrophilic 5\u2010aminolevulinic acid (5\u2010ALA) and hydrophobic tazarotene, facilitating synergistic sonodynamic therapy (SDT) and anti\u2010inflammatory effects. Mechanistically, under ultrasound stimulation, accumulated protoporphyrin IX (PpIX) derived from 5\u2010ALA metabolism generates reactive oxygen species (ROS) that inhibit epidermal proliferation, while tazarotene activates retinoic acid receptor gamma (RAR\u03b3) to exert anti\u2010inflammatory effects. Concurrently, the VISTA\u2010overexpressed membrane enhances anti\u2010inflammatory responses, further amplifying the anti\u2010psoriatic effect. CNP efficacy in a psoriatic mouse model is validated, demonstrating mitigated lesion severity, suppressed epidermal hyperplasia, and reduced inflammatory cytokine levels in skin lesions. Notably, CNPs outperformed non\u2010membrane counterparts in both cellular and animal models, highlighting the anti\u2010psoriatic amplification conferred by the engineered membrane. Overall, this research presents a novel therapeutic strategy for psoriasis management using engineered membrane\u2010coated mesoporous Janus nanoparticles to target keratinocyte proliferation and T cell activation.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202503942","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T07:57:47Z","timestamp":1762934267000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Coating Janus Nanoparticles with Immunoregulatory Protein Embedded Membrane for Enhanced Anti\u2010Inflammatory and Sonodynamic Therapy of Psoriasis"],"prefix":"10.1002","volume":"15","author":[{"given":"Chunpeng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy, and Department of Pharmacy at the Second Affiliated Hospital Harbin Medical University Harbin 150081 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