title: Synergistic dual-ligand doxorubicin liposomes improve targeting and therapeutic efficacy of brain glioma in animals.
abstract: Therapeutic outcome for the treatment of glioma was often limited due to low permeability of delivery systems across the blood-brain barrier (BBB) and poor penetration into the tumor tissue. In order to overcome these hurdles, we developed the dual-targeting doxorubicin liposomes conjugated with cell-penetrating peptide (TAT) and transferrin (T7) (DOX-T7-TAT-LIP) for transporting drugs across the BBB, then targeting brain glioma, and penetrating into the tumor. The dual-targeting effects were evaluated by both in vitro and in vivo experiments. In vitro cellular uptake and three-dimensional tumor spheroid penetration studies demonstrated that the system could not only target endothelial and tumor monolayer cells but also penetrate tumor to reach the core of the tumor spheroids and inhibit the growth of the tumor spheroids. In vivo imaging further demonstrated that T7-TAT-LIP provided the highest tumor distribution. The median survival time of tumor-bearing mice after administering DOX-T7-TAT-LIP was significantly longer than those of the single-ligand doxorubicin liposomes and free doxorubicin. In conclusion, the dual-ligand liposomes comodified with T7 and TAT possessed strong capability of synergistic targeted delivery of payload into tumor cells both in vitro and in vivo, and they were able to improve the therapeutic efficacy of brain glioma in animals.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University , No. 17, Block 3, Southern Renmin Road, Chengdu 610041, P. R. China.
authors.forename: Taili
authors.initials: T
authors.lastname: Zong
authors.forename: Ling
authors.initials: L
authors.lastname: Mei
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.forename: Pengjin
authors.initials: P
authors.lastname: Zhu
authors.forename: Kairong
authors.initials: K
authors.lastname: Shi
authors.forename: Jiantao
authors.initials: J
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Fabao
authors.initials: F
authors.lastname: Gao
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005910:Glioma / Q000188:drug therapy*; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D014168:Transferrin / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D057846:Cell-Penetrating Peptides; D008024:Ligands; D014168:Transferrin; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin