title: A polymeric prodrug of cisplatin based on pullulan for the targeted therapy against hepatocellular carcinoma.
abstract: A polymeric prodrug of cisplatin (CP) with simple chemical structure was synthesized based on pullulan and its therapeutic effects on human hepatocellular carcinoma (HCC) were studied in vitro and in vivo. Briefly, CP was linked to pullulan monosuccinate (SUPA) via coordination bond to form prodrug of CP-SUPA with the CP weight content of 18.7%. CP-SUPA exhibited in vitro sustained releases and strong interactions with genomic DNA. CP-SUPA could effectively inhibit the proliferation of HCC HepG2 cells by promoting the cell apoptosis and arresting the cell cycle, and showed a significantly higher cytotoxicity on HepG2 cells than that on human lung epithelial A549 cells. Compared to free CP, CP-SUPA obviously prolonged the survival times of Balb/c mice after intravenous injection at CP doses of 15 and 30 μmol/kg, and no signs of toxic effects in main tissues were detected by histologic examination. In MHCC-97H tumor-bearing nude mice, CP-SUPA was mainly distributed in the liver and the tumor after 24h post administration and evidently inhibited the tumor growth at CP doses of 3.5 and 7.0 μmol/kg. In conclusion, CP-SUPA was an ideal candidate of polymeric prodrug for the targeted therapy against HCC.
authors: School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Research Center of Basic Medical Science, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors: Yan
authors: Y
authors: Wang
authors: School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Research Center of Basic Medical Science, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China; Cancer Institute and Hospital, Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Huanhuxi Road, Hexi District, Tianjin 300060, PR China.
authors: Yuanyuan
authors: Y
authors: Liu
authors: School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Research Center of Basic Medical Science, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China; Cancer Institute and Hospital, Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Huanhuxi Road, Hexi District, Tianjin 300060, PR China.
authors: Yang
authors: Y
authors: Liu
authors: School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Research Center of Basic Medical Science, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors: Wen
authors: W
authors: Zhou
authors: School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Research Center of Basic Medical Science, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors: Hemei
authors: H
authors: Wang
authors: School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Research Center of Basic Medical Science, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors: Guoyun
authors: G
authors: Wan
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Duxin
authors: D
authors: Sun
authors: School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Research Center of Basic Medical Science, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China; Cancer Institute and Hospital, Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Huanhuxi Road, Hexi District, Tianjin 300060, PR China. Electronic address: zhangning@tijmu.edu.cn.
authors: Ning
authors: N
authors: Zhang
authors: School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Research Center of Basic Medical Science, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China. Electronic address: wangyinsong@tijmu.edu.cn.
authors: Yinsong
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D011355:Prodrugs; D002945:Cisplatin
keywords: Cisplatin; Hepatocellular carcinoma; Prodrug; Pullulan; Targeted therapy