title: Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma.
abstract: The purpose of this study was to develop an efficient dual-ligand based liposomal drug delivery system with targeting specificity as well as properties that would kill melanoma cells. Liposomes modified with transferrin (Tf) and cell-penetrating peptide TAT was prepared, which encapsulated two kinds of chemotherapy drugs, paclitaxel and doxorubicin (Tf/TAT-PTX/DOX-LP). The Tf ligands specifically bind to the overexpressed Tf receptors on the surface of melanoma cells, while the TAT ligands functioned as a classical cell penetrating peptide, helping dual-ligand liposomes be internalized by melanoma cells. The effect of dual-targeting system and "double-drug" combination therapy were evaluated both in vitro and in vivo. In vitro, cellular uptake, intracellular distribution and tumor spheroids penetration studies demonstrated that the system could not only be selectively and efficiently penetrate melanoma cells. Besides, apoptosis staining assay and cytotoxicity showed effective anti-tumor capability and obvious synergistic effect of combination therapy of PTX and DOX. In vivo imaging and fluorescent images of tumor section further demonstrated that Tf/TAT-PTX/DOX-LP had the highest tumor distribution. The results of these experiments demonstrated that double-drug liposomal drug delivery systems (DDS) had both enhanced targeting efficiency and increased therapeutic efficacy.
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P. R. China and.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Yuan
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P. R. China and.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: b Elderly Digestive Department , Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences , Chengdu , China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P. R. China and.
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P. R. China and.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008024:Ligands; D008081:Liposomes; D008545:Melanoma; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D057846:Cell-Penetrating Peptides; D008024:Ligands; D008081:Liposomes; D010455:Peptides; D014168:Transferrin; D004317:Doxorubicin; D017239:Paclitaxel
keywords: Cancer; cell penetrating peptide; chemotherapy; drug delivery system; dual-targeting