Platinum (Pt) drugs are widely used in anti‐cancer treatment although many reports advocated that tumor cells could inactivate Pt drugs via glutathione‐Pt (GSH‐Pt) adducts formation. To date, GSH chelated Pt molecules have not been assessed in cancer treatment because GSH‐Pt adducts are not capable of killing cancer cells, which is widely accepted and well followed. In this report, endogenous biothiol is utilized to precisely synthesize a GSH chelated Pt molecule (Pt₆GS₄). This Pt₆GS₄ molecule can be well taken up by aggressive triple negative breast cancer (TNBC) cells. Subsequently, its metabolites could enter nuclei to interact with DNA, finally the DNA‐Pt complex triggers TNBC cell apoptosis via the p53 pathway. Impressively, high efficacy for anti‐cancer treatment is achieved by Pt₆GS₄ both in vitro and in vivo when compared with traditional first‐line carboplatin in the same dosage. Compared with carboplatin, Pt₆GS₄ keeps tumor bearing mice alive for a longer time and is non‐toxic for the liver and kidneys. This work opens a route to explore polynuclear Pt compound with accurate architecture for enhancing therapeutic effects and reducing systemic toxicity.

中文翻译：

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GSH螯合的Pt分子在抗癌治疗中无效吗？Pt6 GS4的案例研究。

铂（Pt）药物被广泛用于抗癌治疗，尽管许多报道主张肿瘤细胞可以通过谷胱甘肽-Pt（GSH-Pt）加合物的形成使Pt药物失活。迄今为止，尚未对GSH螯合的Pt分子进行癌症治疗的评估，因为GSH-Pt加合物无法杀死癌细胞，这一点已被广泛接受并得到了很好的遵循。在本报告中，利用内源性生物硫醇精确合成GSH螯合的Pt分子（Pt ₆ GS ₄）。铂₆ GS ₄侵袭性三阴性乳腺癌（TNBC）细胞可以很好地吸收这种分子。随后，其代谢物可以进入细胞核与DNA相互作用，最终DNA-Pt复合物通过p53途径触发TNBC细胞凋亡。令人印象深刻的是，与相同剂量的传统一线卡铂相比，Pt ₆ GS ₄在体内和体外均可实现高效的抗癌治疗。与卡铂相比，Pt ₆ GS ₄可使荷瘤小鼠存活更长的时间，并且对肝脏和肾脏无毒。这项工作为探索具有精确结构的多核铂化合物开辟了道路，以增强治疗效果并降低全身毒性。