title: Tailored doxorubicin-hyaluronan conjugate as a potent anticancer glyco-drug: an alternative to prodrug approach.
abstract: Releasibility of doxorubicin from drug-conjugates is believed to be a prerequisite for its anti-cancer activity. Here, a new glyco-drug approach that circumvents the releasibility restriction is reported, opening a new possibility to design efficient, target specific drug delivery system. It is discovered that stable amide coupling of doxorubicin (DOX) tohyaluronan (HA) shows dose dependent cytotoxicity to CD44 positive human coloncancer cells (HCT116) as compared to human breast cancer cells(MCF-7) and mouse fibroblast cells (NIH-3T3), which express less CD44 receptor. This direct conjugation approach is an easy scalable strategy that could be adopted to design innocuous anti-tumor nanoparticle formulations.
authors.affiliation: Department of Chemistry, Ångström Laboratory, Uppsala University, S-75121 Uppsala, Sweden. oommen.op@kemi.uu.se.
authors.forename: Oommen P
authors.initials: OP
authors.lastname: Oommen
authors.forename: Javad
authors.initials: J
authors.lastname: Garousi
authors.forename: Marije
authors.initials: M
authors.lastname: Sloff
authors.forename: Oommen P
authors.initials: OP
authors.lastname: Varghese
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers; D015870:Gene Expression; D006001:Glycoconjugates / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D009928:Organ Specificity; D011355:Prodrugs; D011485:Protein Binding
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D006001:Glycoconjugates; D018960:Hyaluronan Receptors; D011355:Prodrugs; D004317:Doxorubicin; D006820:Hyaluronic Acid
keywords: anticancer therapy; drug delivery; endocytosis; glyco-drug; hyaluronic acid