title: Hydrophobic cavity formed by oligopeptide for doxorubicin delivery based on dendritic poly(L-lysine).
abstract: To deliver anti-cancer drugs to tumors, a hydrophobic cavity was prepared in the dendritic molecule, dendritic poly(L-lysine) of sixth generation (KG6), which was used as a drug carrier. The dendritic molecule was modified with polyethylene glycol (PEG)-linked hydrophobic penta-phenylalanine or penta-alanine. The hydrophobic cavity was formed between the KG6 and PEG chains. The penta-phenylalanine peptide was better in encapsulating doxorubicin (DOX) in the cavity compared with penta-alanine. The loaded DOX was slowly released from the cavity, and it depended on pH. After intravenous injection, the DOX-loaded dendrimers accumulated in the tumor by the enhanced permeability and retention effect, and showed significant suppression of tumor growth without loss of body weight. These results indicate that hydrophobic oligopeptides can be used for forming a hydrophobic cavity in a dendritic molecule for delivery of anti-cancer drugs to tumor sites.
authors.affiliation: a Department of Applied Chemistry and Biochemistry , Graduate School of Science and Technology, Kumamoto University , 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555 , Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Niidome
authors.forename: Hisayo
authors.initials: H
authors.lastname: Yamauchi
authors.forename: Kayo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Naoyama
authors.forename: Kazuto
authors.initials: K
authors.lastname: Watanabe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation*; D065546:Drug Liberation; D006321:Heart / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry*; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D004337:Drug Carriers; D009842:Oligopeptides; D011107:Polylysine; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: dendrimer; doxorubicin; drug delivery; peptide; tumor