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Glabridin (Gla) is a natural isoflavone that inhibits tyrosinase activity, free radical scavenging, and antioxidation. However, its water solubility is poor, and it cannot pass through the human skin barrier alone. Tetrahedral framework nucleic acid (tFNA), a new type of DNA biomaterial, can penetrate cells and tissues and can be used as carriers to deliver small\u2010molecule drugs, polypeptides, and oligonucleotides. This study aimed to develop a compound drug system using tFNA as the carrier to transport Gla and deliver it through the skin to treat pigmentation. Furthermore, we aimed to explore whether tFNA\u2013Gla can effectively alleviate the hyperpigmentation caused by increased melanin production and determine whether tFNA\u2013Gla exerts substantial synergistic effects during treatment. Our results showed that the developed system successfully treated pigmentation by inhibiting regulatory proteins related to melanin production. Furthermore, our findings showed that the system was effective in treating epidermal and superficial dermal diseases. The tFNA\u2010based transdermal drug delivery system can thus develop into novel, effective options for non\u2010invasive drug delivery through the skin barrier.<\/jats:p>","DOI":"10.1111\/cpr.13495","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T09:45:15Z","timestamp":1683107115000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Tetrahedral framework nucleic acid loaded with glabridin: A transdermal delivery system applicated to <scp>anti\u2010hyperpigmentation<\/scp>"],"prefix":"10.1111","volume":"56","author":[{"given":"Jiajun","family":"He","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu 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