title: Galactosylated chitosan-grafted multiwall carbon nanotubes for pH-dependent sustained release and hepatic tumor-targeted delivery of doxorubicin in vivo.
abstract: Carbon nanotubes (CNTs) are well known for their distinctive drug-loading ability that is mainly due to their large surface area, which permits covalent attachment of various target ligands or drug molecules by π-π stacking, allowing them to act as potential tumor-targeting carriers. Herein, we describe the development of galactosylated chitosan-graftedoxidized CNTs (O-CNTs-LCH) for pH-dependent sustained release and hepatic tumor-targeted delivery of doxorubicin (DOX). The in vitro release behavior in aqueous release media of different pH values (5.5, 6.5 and 7.4) verified the pH-dependent sustained release of DOX from O-CNTs-LCH-DOX. Moreover, these nanocarriers exhibited significant in vitro tumor-targeting properties, with a higher cellular uptake efficiency than that of free DOX in HepG2 cells. In addition, the good biocompatibility and low toxicity of O-CNTs-LCH-DOX was demonstrated by evaluating HepG2 cytotoxicity, vascular irritation and the maximum tolerated dose. Moreover, after intravenous administration in mice bearing the H22 tumor, O-CNTs-LCH-DOX showed higher antitumor activity and stronger fluorescent intensity in tumor tissue compared to free DOX. These results indicated the selective hepatic tumor targeting and the therapeutic effect of those nanocarriers.
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Qi
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Rui
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: Zhenghongwu66@cpu.edu.cn.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage*; D005690:Galactose / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D037742:Nanotubes, Carbon
chemical_list: D000903:Antibiotics, Antineoplastic; D037742:Nanotubes, Carbon; D004317:Doxorubicin; D048271:Chitosan; D005690:Galactose
keywords: Carbon nanotubes; Doxorubicin; Galactosylated chitosan; Tumor targeting; pH-dependent release