{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:50:53Z","timestamp":1782111053702,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease worldwide. The one small molecule drug available to patients, tolvaptan, is associated with off\u2010target side effects and high discontinuation rates, necessitating the development of new therapeutic strategies. Previous work has shown that the epigenome is altered in ADPKD; however, the identification and targeting of dysregulated epigenetic modulators has yet to be explored for human ADPKD therapy. Using cells derived from cysts of ADPKD patients, we tested the gene expression of several epigenetic modulators. We found Brd4 and BMi1 are upregulated and observed that their inhibition using small molecule drugs, AZD\u20105153 and PTC\u2010209, significantly slowed the proliferation of ADPKD patient cells. To enhance the delivery of AZD\u20105153 and PTC\u2010209 to renal cells, we loaded the drugs into kidney\u2010targeting micelles (KM) and assessed their therapeutic effects in\u00a0vitro. Combining AZD\u20105153 and PTC\u2010209 in KMs had a synergistic effect on reducing the proliferation in ADPKD patient cells and in a 3D PKD cyst model. These findings were also consistent in murine in\u00a0vitro models using Pkd1 null renal proximal tubule cells. In summary, we demonstrate Brd4 and BMi1 as novel targets in ADPKD and targeting the epigenome using kidney nanomedicine as a novel therapeutic strategy in ADPKD.<\/jats:p>","DOI":"10.1002\/jbm.a.37909","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T03:08:19Z","timestamp":1744168099000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting Dysregulated Epigenetic Modifiers With Kidney\u2010Targeted Nanotherapeutics for Polycystic Kidney Disease"],"prefix":"10.1002","volume":"113","author":[{"given":"Joshua","family":"Giblin","sequence":"first","affiliation":[{"name":"Alfred E. Mann Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowan","family":"Simon","sequence":"additional","affiliation":[{"name":"Alfred E. Mann Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Zarate\u2010Diaz","sequence":"additional","affiliation":[{"name":"Alfred E. Mann Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenton","family":"Lee","sequence":"additional","affiliation":[{"name":"Alfred E. 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Mann Department of Biomedical Engineering University of Southern California  Los Angeles California USA"},{"name":"Department of Medicine, Division of Nephrology and Hypertension Keck School of Medicine, University of Southern California  Los Angeles California USA"},{"name":"Department of Chemical Engineering and Materials Science University of Southern California  Los Angeles California USA"},{"name":"Department of Surgery, Division of Vascular Surgery and Endovascular Therapy Keck School of Medicine, University of Southern California  Los Angeles California USA"},{"name":"Department of Stem Cell Biology and Regenerative Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"StatPearls","author":"Mahboob 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