{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T08:46:39Z","timestamp":1768725999995,"version":"3.49.0"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019405","name":"Kentucky IDeA Networks of Biomedical Research Excellence","doi-asserted-by":"publisher","award":["P20GMI04489"],"award-info":[{"award-number":["P20GMI04489"]}],"id":[{"id":"10.13039\/100019405","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019405","name":"Kentucky IDeA Networks of Biomedical Research Excellence","doi-asserted-by":"publisher","award":["P20GM103436"],"award-info":[{"award-number":["P20GM103436"]}],"id":[{"id":"10.13039\/100019405","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["U01 HL152392"],"award-info":[{"award-number":["U01 HL152392"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Pt-Mal-LHRH is a newly synthesized chemotherapeutic agent that was designed to selectively target the luteinizing hormone-releasing hormone (LHRH) receptor expressed by triple negative breast cancer (TNBC). The aim of this study was to evaluate the therapeutic dosing, tumor reduction efficacy, and selective distribution of Pt-Mal-LHRH in-vivo.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and results<\/jats:title>\n<jats:p>LHRH tissue expression levels in-vivo were investigated using western blotting and LHRH was found to be increased in reproductive tissues (mammary, ovary, uterus). Further, Pt-Mal-LHRH was found to have increased TNBC tumor tissue platinum accumulation compared to carboplatin by inductively coupled plasma mass spectrometry analysis. The platinum family, compound carboplatin, was selected for comparison due to its similar chemical structure and molar equivalent doses were evaluated. Moreover, in-vivo distribution data indicated selective targeting of Pt-Mal-LHRH by enhanced reproductive tissue accumulation compared to carboplatin. Further, TNBC tumor growth was found to be significantly attenuated by Pt-Mal-LHRH compared to carboplatin in both the 4T1 and MDA-MB-231 tumor models. There was a significant reduction in tumor volume in the 4T1 tumor across Pt-Mal-LHRH doses (2.5\u201320 mg\/kg\/wk) and in the MDA-MB-231 tumor at the dose of 10 mg\/kg\/wk in models conducted by an independent contract testing laboratory.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our data indicates Pt-Mal-LHRH is a targeting chemotherapeutic agent towards the LHRH receptor and reduces TNBC tumor growth in-vivo. This study supports drug conjugation design models using the LHRH hormone for chemotherapeutic delivery as Pt-Mal-LHRH was found to be a more selective and efficacious than carboplatin. Further examination of Pt-Mal-LHRH is warranted for its clinical use in TNBCs, along with, other reproductive cancers overexpressing the LHRH receptor.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0287151","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T17:23:58Z","timestamp":1696958638000},"page":"e0287151","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Therapeutic dosing and targeting efficacy of Pt-Mal-LHRH towards triple negative breast cancer"],"prefix":"10.1371","volume":"18","author":[{"given":"Margaret","family":"Ndinguri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Middleton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Unrine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Lui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Rollins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Nienaber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassidy","family":"Spease","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aggie","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0919-0077","authenticated-orcid":true,"given":"Lindsay","family":"Cormier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"issue":"20","key":"pone.0287151.ref001","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1056\/NEJMra1001389","article-title":"Triple-negative breast cancer","volume":"363","author":"W.D. 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Lund","year":"2009","journal-title":"Breast Cancer Res Treat"},{"issue":"5","key":"pone.0287151.ref005","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s11912-021-01041-x","article-title":"Role of Platinums in Triple-Negative Breast Cancer","volume":"23","author":"F. Lynce","year":"2021","journal-title":"Curr Oncol Rep"},{"issue":"8","key":"pone.0287151.ref006","doi-asserted-by":"crossref","first-page":"e0134027","DOI":"10.1371\/journal.pone.0134027","article-title":"Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC\/ESI-MS\/MS) Study for the Identification and Characterization of In Vivo Metabolites of Cisplatin in Rat Kidney Cancer Tissues: Online Hydrogen\/Deuterium (H\/D) Exchange Study","volume":"10","author":"R. 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