Mavroidi Barbara, Lyra Kyriaki Marina, Pispas Stergios, Sideratou Zili, Tsiourvas Dimitris
Institute of Nanoscience and Nanotechnology, National Center for Scientific Research ''Demokritos", 15310 Aghia Paraskevi, Greece.
Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece.
Pharmaceuticals (Basel). 2025 Aug 12;18(8):1189. doi: 10.3390/ph18081189.
: 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. 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. PEI:Cu derivatives are cytotoxic against the human prostate carcinoma metastatic PC3 and DU145 cell lines, even at the lowest tested concentrations of 5 μg/mL, while against the non-cancerous HEK293 cells, all metallopolymer derivatives exhibit insignificant cytotoxicity up concentrations of 50 μg/mL. Their cytotoxic effect is associated with mitochondria membrane potential loss and ROS production increase. Hyperbranched polyethyleneimine-coordinated 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.
在包括前列腺癌在内的各种癌症的血清和肿瘤组织中，铜水平均显著升高。因此，有人提出用铜螯合剂靶向升高的铜水平可能会实现癌症的选择性治疗。因此，几类低分子量的亲脂性铜配位化合物以及新开发的具有适当功能化聚合物的铜配合物，正作为有前景的新型抗癌疗法进行研究。特别是，含金属聚合物或金属聚合物作为抗癌剂或药物递送系统正在被系统地研究。本研究旨在利用超支化聚乙烯亚胺（PEI）强大的铜螯合特性来开发PEI:Cu金属聚合物，并评估它们对几种前列腺癌细胞系的选择性和抗癌特性。制备了一系列PEI/Cu比例能确保溶液中不存在游离铜离子的PEI:Cu配合物，并针对一种人类非癌细胞系和三种转移潜能不断增加的前列腺癌细胞系进行研究。即使在5μg/mL的最低测试浓度下，PEI:Cu衍生物对人前列腺癌转移性PC3和DU145细胞系也具有细胞毒性，而对于非癌性HEK293细胞，所有金属聚合物衍生物在浓度高达50μg/mL时均表现出微不足道的细胞毒性。它们的细胞毒性作用与线粒体膜电位丧失和活性氧生成增加有关。低浓度的超支化聚乙烯亚胺配位铜（II）金属聚合物能在不影响非癌性胚胎肾细胞活力的情况下，选择性地诱导转移性前列腺癌细胞系产生细胞毒性。
