We exploration the in vitro activities of the dinuclear Mn2L2Ac and Mn2L2 complexes (where HL = 2‐{[di(2‐pyridyl)methylamino]‐methyl}phenol), possessing dual superoxide dismutase (SOD) and catalase (CAT) activity, both individually and in conjunction with various Pt(II)‐complexes, either as mixtures or as the Mn2‐Pt adducts. Our findings revealed a notable up to 50% enhancement in the viability of healthy human breast cells, contrasted with a viability decrease as low as 50% in breast cancer cells upon combined treatments with Mn2 SOD mimics and Pt(II) complexes. Specifically, we synthesized and characterized the self‐assembled Mn2‐Pt adducts (isolated Mn2L2Pt and in situ Mn2L2Pt’), linking Mn2L2‐core with the carboxylate group of PtDAPCl2 (dichloro(2,3‐diaminopropionic acid) platinum(II)). The SOD activity of the isolated Mn2L2Pt adduct (kSOD = 1.7 × 107 M−1 s−1) remained intact. We elucidated key mechanisms underlying the observed biological effects. We demonstrated that Mn2‐containing formulations predominantly target mitochondrial processes, differently affecting the proteome of cancerous and healthy cells. They induced downregulation of H2S signaling and expression of mitochondrial complex I and III, as well as increased oxidative phosphorylation pathways and upregulation of EGFR in cancer cells. In contrast, healthy cells showed a decrease in EGFR expression and a moderate enrichment in oxidative phosphorylation pathways.

中文翻译：

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解锁选择性抗癌机制：双核锰超氧化物歧化酶模拟物与 Pt(II) 配合物相结合


我们探索了双核 Mn2L2Ac 和 Mn2L2 复合物（其中 HL = 2-{[二(2-吡啶基)甲基氨基]-甲基}苯酚）的体外活性，具有双重超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 活性，两者单独或与各种 Pt(II) 配合物结合，无论是作为混合物还是作为 Mn2-Pt 加合物。我们的研究结果表明，在使用 Mn2 SOD 模拟物和 Pt(II) 复合物联合治疗后，健康人类乳腺细胞的活力显着提高了 50%，而乳腺癌细胞的活力仅下降了 50%。具体来说，我们合成并表征了自组装的 Mn2-Pt 加合物（分离的 Mn2L2Pt 和原位 Mn2L2Pt'），将 Mn2L2 核心与 PtDAPCl2（二氯（2,3-二氨基丙酸）铂（II））的羧酸酯基团连接起来。分离的 Mn2L2Pt 加合物 (kSOD = 1.7 × 107 M−1 s−1) 的 SOD 活性保持完整。我们阐明了观察到的生物效应背后的关键机制。我们证明，含 Mn2+ 的制剂主要针对线粒体过程，对癌细胞和健康细胞的蛋白质组有不同的影响。它们诱导癌细胞中 H2S 信号传导和线粒体复合物 I 和 III 表达的下调，以及氧化磷酸化途径的增加和 EGFR 的上调。相比之下，健康细胞的 EGFR 表达降低，氧化磷酸化途径适度富集。