Targeting cisplatin to the sites of action and decreasing its side effects are still major challenges. Here, we introduced a polyglutamic acid-platinum(IV) prodrug nanoconjugates (γ-PGA-CA-Pt(IV)) constructed by polyglutamic acid and modified platinum(IV) prodrug to reserve the anti-tumor efficacy of cisplatin with decreased side effects. We describe the synthesis, physico-chemical characterization, and redox- and pH-sensitive releasing behavior of the nanoconjugate. In vitro studies revealed that, when incubated with glutathione in advance, the γ-PGA-CA-Pt(IV) nanoconjugate induced significant apoptosis in human breast carcinoma MCF-7 cells. From in vivo antitumor efficacy evaluation, the γ-PGA-CA-Pt(IV) nanoconjugate obviously improved the survival rate of tumor-bearing mice with inhibition of the tumor growth compared with cisplatin. Meanwhile, the nanoconjugates showed remarkable improved safety profile than the free cisplatin.

将顺铂靶向作用部位并减少其副作用仍然是主要挑战。在这里，我们介绍了一种由聚谷氨酸和修饰的铂（IV）前药构建的聚谷氨酸-铂（IV）前药纳米共轭物（γ-PGA-CA-Pt（IV）），以保留顺铂的抗肿瘤功效并减少副作用。我们描述了纳米共轭物的合成，理化性质以及氧化还原和pH敏感释放行为。体外研究表明，当预先与谷胱甘肽一起孵育时，γ-PGA-CA-Pt（IV）纳米共轭物可诱导人乳腺癌MCF-7细胞明显凋亡。通过体内抗肿瘤功效评估，与顺铂相比，γ-PGA-CA-Pt（IV）纳米复合物显着提高了荷瘤小鼠的存活率，并且抑制了肿瘤的生长。与此同时，