title: Tumor cells-specific targeting delivery achieved by A54 peptide functionalized polymeric micelles.
abstract: The delivery of all of administrated chemotherapeutics into tumor cells is an extreme object for tumor targeting therapy to enhance the curative effect and eliminate the side effect. However, until now, the targeting delivery has only partial been realized by passive targeting, which was called "enhanced permeability and retention" effect, and only few targeting delivery system was commercialized. Here, we designed and synthesized a hepatocarcinoma-binding peptide (A54 peptide, which was identified from a phage-display random peptide library) functionalized and PEGylated stearic acid grafted chitosan (A54-PEG-CS-SA) micelles for targeting therapy of doxorubicin. The A54-PEG-CS-SA micelles presented special internalization ability into human hepatoma cells (BEL-7402) when the cells were co-incubated with normal liver cells in vitro, and high distribution ability to liver and hepatoma tissue in vivo. In vitro and in vivo anti-tumor activity results showed that A54-PEG-CS-SA micelles loading doxorubicin treatments suppressed tumor growth more effectively and reduced toxicity compared with commercial adriamycin injection.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China. duyongzhong@zju.edu.cn
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Du
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Cai
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: You
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Hu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D013229:Stearic Acids / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D009842:Oligopeptides; D013229:Stearic Acids; D011092:Polyethylene Glycols; D004317:Doxorubicin; D048271:Chitosan