{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:16:57Z","timestamp":1773271017711,"version":"3.50.1"},"reference-count":79,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCSR internal project","award":["EE12808"],"award-info":[{"award-number":["EE12808"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Copper levels are significantly elevated in both the sera and tumor tissues of various cancers, including prostate cancer. It has therefore been suggested that targeting the elevated copper levels with copper chelators could lead to selective cancer treatment. Thus, several classes of low molecular weight copper-coordinating lipophilic compounds, as well as the newly developed copper complexes of appropriately functionalized polymers, are being investigated as promising novel anticancer therapeutics. Particularly, metal-containing polymers, or metallopolymers, are systematically investigated as anticancer agents or as drug delivery systems. This study aims to utilize the strong copper-chelating properties of hyperbranched polyethyleneimine (PEI) to develop PEI:Cu metallopolymers and evaluate their selectivity and anticancer properties against several prostate cancer cell lines. Methods: A series of PEI:Cu complexes at PEI\/Cu ratios that ensure that no free copper ions are present in the solution are prepared and investigated against a human non-cancerous cell line and three prostate cancer cell lines of increasing metastatic potential. Results: PEI:Cu derivatives are cytotoxic against the human prostate carcinoma metastatic PC3 and DU145 cell lines, even at the lowest tested concentrations of 5 \u03bcg\/mL, while against the non-cancerous HEK293 cells, all metallopolymer derivatives exhibit insignificant cytotoxicity up concentrations of 50 \u03bcg\/mL. Their cytotoxic effect is associated with mitochondria membrane potential loss and ROS production increase. Conclusions: Hyperbranched polyethyleneimine\u2013coordinated copper(II) metallopolymers, at low concentrations, selectively induce cytotoxicity in metastatic prostate cancer cell lines without compromising the viability of non-cancerous embryonic kidney cells.<\/jats:p>","DOI":"10.3390\/ph18081189","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T15:51:02Z","timestamp":1755013862000},"page":"1189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hyperbranched Polyethyleneimine\u2013Coordinated Copper(II) Metallopolymers with Preferential Targeting to Prostate Cancer Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Barbara","family":"Mavroidi","sequence":"first","affiliation":[{"name":"Institute of Nanoscience and Nanotechnology, National Center for Scientific Research \u2018\u2018Demokritos\u201d, 15310 Aghia Paraskevi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyriaki Marina","family":"Lyra","sequence":"additional","affiliation":[{"name":"Institute of Nanoscience and Nanotechnology, National Center for Scientific Research \u2018\u2018Demokritos\u201d, 15310 Aghia Paraskevi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5347-7430","authenticated-orcid":false,"given":"Stergios","family":"Pispas","sequence":"additional","affiliation":[{"name":"Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9314-2520","authenticated-orcid":false,"given":"Zili","family":"Sideratou","sequence":"additional","affiliation":[{"name":"Institute of Nanoscience and Nanotechnology, National Center for Scientific Research \u2018\u2018Demokritos\u201d, 15310 Aghia Paraskevi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitris","family":"Tsiourvas","sequence":"additional","affiliation":[{"name":"Institute of Nanoscience and Nanotechnology, National Center for Scientific Research \u2018\u2018Demokritos\u201d, 15310 Aghia Paraskevi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.2741\/1424","article-title":"Copper Storage Diseases: Menkes, Wilsons, and Cancer","volume":"9","author":"Daniel","year":"2004","journal-title":"Front. 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