Redox-sensitive polyglutamic acid-platinum(IV) prodrug grafted nanoconjugates for efficient delivery of cisplatin into breast tumor

Targeting cisplatin to the sites of action and decreasing its side effects are still major challenges. Here, we introduced a polyglutamic acidplatinum(IV) prodrug nanoconjugates (gamma-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 redoxand pH-sensitive releasing behavior of the nanoconjugate. In vitro studies revealed that, when incubated with glutathione in advance, the gamma-PGACA-Pt(IV) nanoconjugate induced significant apoptosis in human breast carcinoma MCF-7 cells. From in vivo antitumor efficacy evaluation, the gamma-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. (C) 2020 Elsevier Inc. All rights reserved.