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To improve drug efficiency without increasing dose, kidney-specific drug delivery may be used. Mesoscale nanoparticles (MNP) selectively target the proximal tubules in rodents. We explored whether MNPs can target cystic kidney tubules and whether rapamycin-encapsulated-MNPs (RapaMNPs) can slow cyst growth in\n                    <jats:italic>Pkd1<\/jats:italic>\n                    knockout (KO) mice. MNP was intravenously administered in adult\n                    <jats:italic>Pkd1<\/jats:italic>\n                    KO mice. Serum and organs were harvested after 8, 24, 48 or 72\u00a0h to measure MNP localization, mTOR levels, and rapamycin concentration.\n                    <jats:italic>Pkd1<\/jats:italic>\n                    KO mice were then injected bi-weekly for 6\u00a0weeks with RapaMNP, rapamycin, or vehicle to determine drug efficacy on kidney cyst growth. Single MNP injections lead to kidney-preferential accumulation over other organs, specifically in tubules and cysts. Likewise, one RapaMNP injection resulted in higher drug delivery to the kidney compared to the liver, and displayed sustained mTOR inhibition. Bi-weekly injections with RapaMNP, rapamycin or vehicle for 6\u00a0weeks resulted in inconsistent mTOR inhibition and little change in cyst index, however. MNPs serve as an effective short-term, kidney-specific delivery system, but long-term RapaMNP failed to slow cyst progression in\n                    <jats:italic>Pkd1<\/jats:italic>\n                    KO mice.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-65830-7","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T04:03:58Z","timestamp":1719893038000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Rapamycin-encapsulated nanoparticle delivery in polycystic kidney disease mice"],"prefix":"10.1038","volume":"14","author":[{"given":"Shinobu","family":"Yamaguchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randee","family":"Sedaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chintan","family":"Kapadia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifeng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Shan","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor F.","family":"Berryhill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Landon","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Lovelady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasin","family":"Oduk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan M.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar A.","family":"Jaimes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Heller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamitsu","family":"Saigusa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"65830_CR1","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1146\/annurev.med.60.101707.125712","volume":"60","author":"PC Harris","year":"2009","unstructured":"Harris, P. 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