{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T07:23:25Z","timestamp":1787383405213,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","award":["CUP B93D21010860004\u2010CN 00000041"],"award-info":[{"award-number":["CUP B93D21010860004\u2010CN 00000041"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Activating KRAS mutations, particularly G12 variants, are key drivers in pancreatic ductal adenocarcinoma and other cancers. While KRAS was historically considered undruggable, mutant\u2010specific inhibitors, including non\u2010covalent KRAS G12D inhibitor MRTX1133, have emerged. However, efficacy and resistance remain challenges. We utilized a stimuli\u2010sensitive, ferritin\u2010derived nanomedicine platform to encapsulate high concentrations of MRTX1133, aiming for targeted delivery of the drug to KRAS\u2010mutated pancreatic ductal adenocarcinoma cells. This platform, designed for enhanced biodistribution and reduced off\u2010target effects, achieved a major efficacy over free MRTX1133 in 2D models regarding cell proliferation and KRAS inhibition pathway and, in 3D spheroid models, specifically concerning cell death. Efficacy in patient\u2010derived organoids was comparable. This study demonstrates the potential of this nanomedicine platform for targeted delivery of KRAS mutant\u2010specific inhibitors to human tumors.<\/jats:p>","DOI":"10.1002\/pro.70444","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:29:56Z","timestamp":1768912196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ferritin\u2010based nanocarrier delivery of\n                    <scp>KRAS G12D<\/scp>\n                    inhibitor in pancreatic adenocarcinoma cells and patient\u2010derived organoids: A novel approach for treatment"],"prefix":"10.1002","volume":"35","author":[{"given":"Annalisa Pia","family":"Abbinantefina","sequence":"first","affiliation":[{"name":"Department of Anatomical, Histological, Forensic &amp; Orthopaedic Sciences, Section of Histology and Medical Embryology Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Tito","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic &amp; Orthopaedic Sciences, Section of Histology and Medical Embryology Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Masciarelli","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic &amp; Orthopaedic Sciences, Section of Histology and Medical Embryology Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Tisci","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology Italian National Research Council, IBPM\u2010CNR  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierpaolo","family":"Ceci","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology Italian National Research Council, IBPM\u2010CNR  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Falvo","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology Italian National Research Council, IBPM\u2010CNR  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Ruta","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Human Anatomy Catholic University of the Sacred Heart  Rome Italy"},{"name":"GSTeP Organoids Research Core Facility Fondazione Policlinico A. Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Panzeri","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Human Anatomy Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Sette","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Human Anatomy Catholic University of the Sacred Heart  Rome Italy"},{"name":"GSTeP Organoids Research Core Facility Fondazione Policlinico A. Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-7912","authenticated-orcid":false,"given":"Francesco","family":"Fazi","sequence":"additional","affiliation":[{"name":"Department of Wellbeing, Health and Environmental Sustainability (BeSSA), Sapienza University of Rome, Rieti, c\/o Department of Anatomical, Histological, Forensic &amp; Orthopaedic Sciences, Section of Histology and Medical Embryology Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Colotti","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology Italian National Research Council, IBPM\u2010CNR  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol31040150"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2105281"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.09.017"},{"issue":"11","key":"e_1_2_10_5_1","article-title":"Mitoxantrone\u2010loaded nanoferritin slows tumor growth and improves the overall survival rate in a subcutaneous pancreatic cancer mouse model","volume":"9","author":"Conti G","year":"2021","journal-title":"Biomedicine"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-24-0177"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12100992"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-01851-8"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.02.025"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b02052"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.08.010"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e20770"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03063-y"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02007-7"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2021.06.013"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-23-2504"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06653-2"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26213-y"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2023.102110"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12796"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101411"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-39608-2"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0365"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-080819-033145"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.142843"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.64233"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01688"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-2098"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1884-x"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.70444","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pro.70444","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.70444","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T06:38:02Z","timestamp":1787380682000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.70444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/pro.70444"],"URL":"https:\/\/doi.org\/10.1002\/pro.70444","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]},"assertion":[{"value":"2025-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70444"}}