title: Synergistic targeted delivery of payload into tumor cells by dual-ligand liposomes co-modified with cholesterol anchored transferrin and TAT.
abstract: This study was mainly focused on developing a dual-ligand liposomal delivery system to enhance both targeting specificity and cellular uptake. The specific ligand transferrin (TF) and the cationic cell-penetrating peptide TAT were connected with cholesterol via a polyethylene glycol (PEG) spacer to prepare the dual-ligand liposomes (TAT/TF-PEG-LP). Then the in vitro cellular uptake by three kinds of cells that possessed different expressing levels of transferrin receptor (TFR) and the in vivo delivery efficiency were evaluated. Compared to the single-ligand TAT or TF modified liposomes (TAT-PEG-LP or TF-PEG-LP), TAT/TF-PEG-LP exhibited the enhanced cellular uptake and selectivity via the synergistic effect of both ligands in vitro. The ex vivo fluorescence imaging of tumors, the qualitative observation of tumor frozen section and the quantitative determination of cellular uptake in tumor tissues altogether showed the in vivo delivery efficiency of TAT/TF-PEG-LP was higher than that of other liposomes. In conclusion, the dual-ligand liposomes co-modified with TF and TAT possessed a strong capability for synergistic targeted delivery of payload into tumor cells both in vitro and in vivo.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yayuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Qin
authors.forename: Yujia
authors.initials: Y
authors.lastname: Yin
authors.forename: Wenmin
authors.initials: W
authors.lastname: Yuan
authors.forename: Yuting
authors.initials: Y
authors.lastname: Yang
authors.forename: Yafei
authors.initials: Y
authors.lastname: Xie
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D001692:Biological Transport; D002463:Cell Membrane Permeability; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008081:Liposomes; D008113:Liver Neoplasms / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D011990:Receptors, Transferrin / Q000378:metabolism*; D013678:Technology, Pharmaceutical / Q000379:methods; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D008081:Liposomes; D010446:Peptide Fragments; D011990:Receptors, Transferrin; D014168:Transferrin; D054322:tat Gene Products, Human Immunodeficiency Virus; D011092:Polyethylene Glycols; D002784:Cholesterol
keywords: Cell penetrating peptide; Dual-ligand; Liposomes; Synergistic effect; Transferrin