Glycosylated Platinum(IV) Complexes as Substrates for Glucose Transporters (GLUTs) and Organic Cation Transporters (OCTs) Exhibited Cancer Targeting and Human Serum Albumin Binding Properties for Drug Delivery
Glycosylated Platinum(IV) Complexes as Substrates for Glucose Transporters (GLUTs) and Organic Cation Transporters (OCTs) Exhibited Cancer Targeting and Human Serum Albumin Binding Properties for Drug Delivery
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糖基化铂 (IV) 复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，表现出癌症靶向性和人血清白蛋白结合特性，可用于药物输送
DOI：
10.1021/acs.jmedchem.7b00433
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发表时间：
2017-07-13
影响因子：
7.3
通讯作者：
Wang, Xin
中科院分区：
文献类型：
--
作者：
Ma, Jing;Wang, Qingpeng;Wang, Xin
首次合成了糖基化铂（IV）配合物作为GLUT和OCT的底物，并在体外和体内测定了其细胞毒性和详细机制。半乳糖苷Pt（IV）、葡萄糖苷Pt（IV）和甘露糖苷Pt（W）具有高度细胞毒性，并在体外和体内显示出特异性的癌症靶向特性。糖基化铂（W）络合物5、6、7和8（IC 50 0.24-3.97 μ M）具有更好的抗肿瘤活性，比阳性对照顺铂（1a）、奥沙利铂（3a）和沙铂（5a）高近166倍。十六烷链的存在允许与人血清白蛋白（HSA）结合用于药物递送，这不仅增强了惰性铂（IV）前药的稳定性，而且还降低了它们被人全血中存在的还原剂还原。与非癌细胞（293 T和3 T3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是潜在安全的。
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(W) were highly cytotoxic and showed specific cancer-targeting properties in vitro and in vivo. Glycosylated platinum(W) complexes 5, 6, 7, and 8 (IC50 0.24-3.97 mu M) 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.