{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T12:55:52Z","timestamp":1788612952509,"version":"build-2803163510"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2023-00275456"],"award-info":[{"award-number":["RS-2023-00275456"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 HL143403, R01 CA254110, U01 CA274304"],"award-info":[{"award-number":["U01 HL143403, R01 CA254110, U01 CA274304"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013415","name":"Purdue University Center for Cancer Research","doi-asserted-by":"publisher","award":["P30 CA023168"],"award-info":[{"award-number":["P30 CA023168"]}],"id":[{"id":"10.13039\/100013415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1TR004402"],"award-info":[{"award-number":["UM1TR004402"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Over 90% of pancreatic ductal adenocarcinoma (PDAC) patients involve\n KRAS<\/jats:italic>\n mutations (\n KRAS<\/jats:italic>\n MUT<\/jats:sup>\n ), for which current treatment options are limited. Statins, commonly used to lower cholesterol, have demonstrated certain selective toxicity towards\n KRAS<\/jats:italic>\n -transformed cells, prompting the question of whether statin-based conjugates could achieve selective uptake specifically in\n KRAS<\/jats:italic>\n MUT<\/jats:sup>\n cells. To investigate this, we synthesized statin-dye conjugates by attaching a fluorescent dye (Cy5.5) to two statins: simvastatin and pravastatin, aiming to assess whether selective uptake indeed occurs. Our findings revealed that these conjugates exhibited markedly enhanced uptake in\n KRAS<\/jats:italic>\n MUT<\/jats:sup>\n cells compared to\n KRAS<\/jats:italic>\n wild-type (\n KRAS<\/jats:italic>\n WT<\/jats:sup>\n ) cells. We evaluated the uptake of these conjugates in both\n KRAS<\/jats:italic>\n MUT<\/jats:sup>\n and\n KRAS<\/jats:italic>\n WT<\/jats:sup>\n cells and examined their potential to selectively target\n KRAS<\/jats:italic>\n MUT<\/jats:sup>\n pancreatic cancer cells (PCCs) using an engineered PDAC tumor model co-cultured with PCCs and cancer-associated fibroblasts (CAFs). Our findings indicate that\n KRAS<\/jats:italic>\n MUT<\/jats:sup>\n cancer cells exhibited higher uptake of statin-Cy5.5 conjugates\n via<\/jats:italic>\n enhanced macropinocytosis compared to\n KRAS<\/jats:italic>\n WT<\/jats:sup>\n cancer cells and CAFs. We also found enhanced uptake of the statin-Cy5.5 conjugate in MCF10A cells with\n PTEN<\/jats:italic>\n deficiency, a condition known to elevate macropinocytosis, compared to control MCF10A cells with wild-type\n PTEN<\/jats:italic>\n . Notably, in the PCC and CAF co-culture model, the pravastatin-Cy5.5 conjugate selectively killed\n KRAS<\/jats:italic>\n MUT<\/jats:sup>\n PCCs without affecting the\n KRAS<\/jats:italic>\n WT<\/jats:sup>\n CAFs. These findings highlight the unique synergistic potential of statin-Cy5.5\u2014distinct from either component alone\u2014as targeted delivery vehicles for\n KRAS<\/jats:italic>\n MUT<\/jats:sup>\n cancer therapy.\n <\/jats:p>","DOI":"10.1371\/journal.pone.0340189","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T18:33:35Z","timestamp":1767983615000},"page":"e0340189","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Statin-dye conjugates for selective targeting of KRAS mutant cancer cells"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-6398","authenticated-orcid":true,"given":"Hye-ran","family":"Moon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenying","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Kyung","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeyoun","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Taek","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean J.","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ick Chan","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bumsoo","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3422-3272","authenticated-orcid":true,"given":"Ju Hee","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"pone.0340189.ref001","doi-asserted-by":"crossref","unstructured":"Siegel RL, Giaquinto AN, Jemal A. 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