Glycosylated platinum(IV) complexes were synthesized as substrates for GLUTs and OCTs for the first time, and the cytotoxicity and detailed mechanism were determined in vitro and in vivo. Galactoside Pt(IV), glucoside Pt(IV), and mannoside Pt(IV) were highly cytotoxic and showed specific cancer-targeting properties in vitro and in vivo. Glycosylated platinum(IV) complexes 5, 6, 7, and 8 (IC₅₀ 0.24–3.97 μM) had better antitumor activity of nearly 166-fold higher than the positive controls cisplatin (1a), oxaliplatin (3a), and satraplatin (5a). The presence of a hexadecanoic chain allowed binding with human serum albumin (HSA) for drug delivery, which not only enhanced the stability of the inert platinum(IV) prodrugs but also decreased their reduction by reductants present in human whole blood. Their preferential accumulation in cancer cells compared to noncancerous cells (293T and 3T3 cells) suggested that they were potentially safe for clinical therapeutic use.

中文翻译：

---

糖基化铂（IV）配合物作为葡萄糖转运蛋白（GLUT）和有机阳离子转运蛋白（OCT）的底物展示了针对药物的靶向癌症和人血清白蛋白结合特性

首次合成了糖基化的铂（IV）复合物作为GLUT和OCT的底物，并在体内和体外确定了细胞毒性和详细的机制。半乳糖苷Pt（IV），葡萄糖苷Pt（IV）和甘露糖苷Pt（IV）具有高度的细胞毒性，并在体外和体内显示出特定的靶向癌症特性。糖基化铂（IV）配合物5，6，7，和8（IC ₅₀ 0.24-3.97μM）具有近166倍顺铂阳性对照（较高的更好的抗肿瘤活性1A），奥沙利铂（图3a），和沙铂（5a中）。十六烷链的存在允许与人血清白蛋白（HSA）结合以进行药物递送，这不仅增强了惰性铂（IV）前药的稳定性，而且还减少了人全血中存在的还原剂对它们的还原作用。与非癌细胞（293T和3T3细胞）相比，它们在癌细胞中的优先积累表明，它们对于临床治疗用途具有潜在的安全性。