title: Intracellular delivery of mitomycin C with targeted polysaccharide conjugates against multidrug resistance.
abstract: Intracellular targeted conjugates of xyloglucan and mitomycin C (MMC) were synthesized with a lysosomally degradable peptide spacer and galactosamine, a terminal moiety that can be used to target polymeric conjugates to hepatoma. The content of the MMC was about 3.5% (mol) in this conjugate. In an in vitro cytotoxicity experiment, the targeted prodrugs have higher cytotoxicity than free MMC against the drug resistant HepG2 cells. In a human tumor xenograft nude mouse model, the targeted prodrugs generated higher therapeutic effect than non-targeted prodrugs or free MMC. Together, these results suggest that targeted prodrugs, which have improved transfer efficiency and hepatocyte specificity, may be useful for the reversion of drug resistant HepG2 cells.
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology (Ministry of Education), College of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China. caoyu@iccas.ac.cn
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Didi
authors.initials: D
authors.lastname: Chen
authors.forename: Peiguang
authors.initials: P
authors.lastname: Zhao
authors.forename: Lina
authors.initials: L
authors.lastname: Liu
authors.forename: Xueying
authors.initials: X
authors.lastname: Huang
authors.forename: Chao
authors.initials: C
authors.lastname: Qi
authors.forename: Yanli
authors.initials: Y
authors.lastname: Liu
authors.forename: Hongxuan
authors.initials: H
authors.lastname: He
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Sha
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005688:Galactosamine / Q000737:chemistry / Q000494:pharmacology; D005936:Glucans / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000008:administration & dosage* / Q000737:chemistry; D011355:Prodrugs / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D014990:Xylans / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D005936:Glucans; D011355:Prodrugs; D014990:Xylans; C029353:xyloglucan; D016685:Mitomycin; D005688:Galactosamine