Mono-functionalized glycosylated platinum(IV) complexes possessed both pH and redox dual-responsive properties: Exhibited enhanced safety and preferentially accumulated in cancer cells in vitro and in vivo.
A serious of carbohydrate-conjugated platinum(IV) complexes in the form Pt(L2)(A2)(OH)R based on the clinical drug cisplatin and oxaliplatin were designed, synthesized and evaluated as antitumor agents in vitro and in vivo. The conjugates possessing both pH and redox dual-responsive properties exhibited more potent cytotoxicity in seven different human cancer cell lines and lower toxicity to the normal 3T3 cells than cisplatin, oxaliplatin and even the reported bis-functionalized glycosylated platinum(IV) complexes indicating the enhanced safety of the sugar conjugates. Cellular drug uptake and DNA platination were also superior to cisplatin, oxaliplatin and the reported bis-functionalized ones. Peak current of B7 and B8 with the scan rate of 200mv/s at the concentration of 0.08 mM was 5-fold higher at pH 6.4 than the pH 7.4, indicating that carbohydrate-conjugated mono-functionalized platinum(IV) complexes possessed both pH and redox dual-responsive properties in the cancer cells. The in vivo assays demonstrated that the Pt(IV) compounds could inhibit the growth of MCF-7 tumour and exert more safety than oxaliplatin.
College of Pharmacy, State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, PR China.
Jing
J
Ma
College of Pharmacy, State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, PR China.
Xiande
X
Yang
College of Pharmacy, State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, PR China.
Wenpei
W
Hao
College of Pharmacy, State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, PR China.
Zhonglv
Z
Huang
College of Pharmacy, State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, PR China; Tianjin Key Laboratory of Molecular Drug Research, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, PR China. Electronic address: wangxinnk@nankai.edu.cn.
Xin
X
Wang
College of Pharmacy, State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, PR China; Tianjin Key Laboratory of Molecular Drug Research, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, PR China. Electronic address: pwang@nankai.edu.cn.
Peng George
PG
Wang
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology*; D000077150:Oxaliplatin; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002945:Cisplatin
Antitumor; Cancer; Glycosylation; Metal complexe; Platinum