title: The targeting mechanism of DHA ligand and its conjugate with Gemcitabine for the enhanced tumor therapy.
abstract: Docosahexaenoic acid (DHA), an omega-3 C22 natural fatty acid serving as a precursor for metabolic and biochemical pathways, was reported as a targeting ligand of anticancer drugs. However, its tumor targeting ability and mechanism has not been claimed. Here we hypothesized that the uptake of DHA by tumor cells is related to the phosphatidylethanolamine (PE) contents in cell membranes. Thus, in this manuscript, the tumor-targeting ability of DHA was initially demonstrated in vitro and in vivo on different tumor cell lines by labeling DHA with fluorescence dyes. Subsequently, the tumor targeting ability was then correlated with the contents of PE in cell membranes to study the uptake mechanism. Further, DHA was conjugated with anticancer drug gemcitabine (DHA-GEM) for targeted tumor therapy. Our results demonstrated that DHA exhibited high tumor targeting ability and PE is the main mediator, which confirmed our hypothesis. The DHA-GEM displayed enhanced therapeutic efficacy than that of GEM itself, indicating that DHA is a promising ligand for tumor targeted therapy.
authors.affiliation: Department of Biomedical Engineering, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University.
authors.forename: Siwen
authors.initials: S
authors.lastname: Li
authors.forename: Jingyi
authors.initials: J
authors.lastname: Qin
authors.forename: Caiping
authors.initials: C
authors.lastname: Tian
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.forename: Guissi
authors.initials: G
authors.lastname: Fida
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Qian
authors.forename: Wei R
authors.initials: WR
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University.
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011897:Random Allocation; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D008024:Ligands; D010714:Phosphatidylethanolamines; D003841:Deoxycytidine; D004281:Docosahexaenoic Acids; C483858:phosphatidylethanolamine; D000093542:Gemcitabine