title: Self-assembled targeted nanoparticles based on transferrin-modified eight-arm-polyethylene glycol-dihydroartemisinin conjugate.
abstract: Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, an efficient tumor targeted-nanoparticle delivery system, transferrin-eight-arm-polyethylene glycol-dihydroartemisinin nanoparticles (TF-8arm-PEG-DHA NPs) for the vehiculation of dihydroartemisinin (DHA) was first prepared and evaluated for its targeting efficiency and cytotoxicity in vitro and in vivo to Lewis lung carcinoma (LLC) cells, which overexpress transferrin receptors (TFRs). The synthesized TF-8arm-PEG-DHA NPs had high solubility (~102 fold of free DHA), relatively high drug loading (~10 wt% DHA), long circulating half-life and moderate particle size (~147 nm). The in vitro cytotoxicity and in vivo tumor growth inhibition studies in LLC-tumor bearing mice confirmed the enhanced efficacy of TF-modified 8arm-PEG-DHA NPs compared to free DHA and non-modified 8arm-PEG-DHA NPs. All these results together supported that the formulation developed in this work exhibited great potential as an effective tumor targeting delivery system for insoluble anticancer drugs.
authors.affiliation: Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, P. R. China.
authors.forename: Kefeng
authors.initials: K
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Pulp &Paper, Tianjin University of Science &Technology, Tianjin 300457, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dai
authors.affiliation: Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, P. R. China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, P. R. China.
authors.forename: Luying
authors.initials: L
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, P. R. China.
authors.forename: Jiandu
authors.initials: J
authors.lastname: Lei
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D008024:Ligands; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011990:Receptors, Transferrin; D012995:Solubility; D014018:Tissue Distribution; D014168:Transferrin / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D008024:Ligands; D011990:Receptors, Transferrin; D014168:Transferrin; D011092:Polyethylene Glycols; C039060:artenimol