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Mild thermal stimulation promises safer uptake, yet achieving precise temperature control is inconvenient, and its transdermal efficacy and mechanisms remain unclear. A heat\u2010responsive cream made from a stearic acid\u2010lauric acid eutectic, polydopamine (PDA) nanoparticles, glycerin, and drugs is introduced. This cream maintains skin temperature \u223c40\u00a0\u00b0C under simulated sunlight by absorbing excess heat through phase change, preventing overheating while preserving the effectiveness of the drug without requiring manual adjustments. Mild photothermal treatment boosted penetration of PDA nanoparticles (2.4\u2013406.9\u00a0nm) by 5.5\u20137.1\u2010fold, and achieved 28.9\u2010, 24.6\u2010, and 10.7\u2010fold increase of fluorescent signals in dermis for rhodamine B (RB), RB\u2010labeled 5 or 20\u00a0kDa dextran versus nonheated controls, respectively. Mechanistic studies revealed that the photothermal effect enhances transdermal delivery by inducing micropores on the skin and through the transappendageal route. Moreover, insulin delivered through this strategy reduced blood glucose by 75% in diabetic mice, and co\u2010delivery of PDA NPs with methotrexate significantly improved psoriasis lesions. This self\u2010regulating platform uniquely unites precise thermal control and dual\u2010pathway enhancement, offering a generalizable route for enhancing transdermal delivery efficiency.<\/jats:p>","DOI":"10.1002\/adma.202416017","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T13:30:22Z","timestamp":1759239022000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Heat\u2010Responsive Phase\u2010Change Cream Broadly Enhances Transdermal Delivery Through a Mild Photothermal Strategy"],"prefix":"10.1002","volume":"38","author":[{"given":"Rui","family":"Geng","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica Hubei Research Center for Biomaterials and Medical Protective Materials School of Chemistry and Chemical Engineering Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyue","family":"Xiao","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica Hubei Research Center for Biomaterials and Medical Protective Materials School of Chemistry and Chemical Engineering Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duohang","family":"Bi","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica Hubei Research Center for Biomaterials and Medical Protective Materials School of Chemistry and Chemical Engineering Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica Hubei Research Center for Biomaterials and Medical Protective Materials School of Chemistry and Chemical Engineering Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica Hubei Research Center for Biomaterials and Medical Protective Materials School of Chemistry and Chemical Engineering Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7503-3910","authenticated-orcid":false,"given":"Yijing","family":"Liu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica Hubei Research Center for Biomaterials and Medical Protective Materials School of Chemistry and Chemical Engineering Huazhong University of Science and Technology  Wuhan 430074 China"},{"name":"Shenzhen Huazhong University of Science and Technology Research Institute  Shenzhen 518057 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica Hubei Research Center for Biomaterials and Medical Protective Materials School of Chemistry and Chemical Engineering Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43067-8"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202304582"},{"key":"e_1_2_8_1_3","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202307104"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.08.050"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202412160"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.183"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202409416"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2024.114138"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202403758"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202300066"},{"key":"e_1_2_8_4_3","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202311246"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-020-00823-3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202306944"},{"key":"e_1_2_8_7_1","first-page":"67","volume":"14","author":"Vaseem R. 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