title: Lung cancer gene therapy: Transferrin and hyaluronic acid dual ligand-decorated novel lipid carriers for targeted gene delivery.
abstract: To achieve lung cancer gene therapy, nanocarriers decorated with different ligands were used. Surface decoration and nanoparticulate system will assist in targeting the gene to specific cells and tissues, such as cancers and diseased organs. The aim of this research was to develop a dual ligand-decorated nanocarriers, which could target the tumor cells through receptor-mediated pathways to increase the uptake of genetic materials. Transferrin (Tf) and hyaluronic (HA) containing polyethylene glycol-distearoylphosphatidylethanolamine (Tf-PEG-DSPE and HA-PEG-DSPE) ligands were synthesized. Novel Tf and HA ligand-decorated, plasmid-enhanced green fluorescent protein loaded nanostructured lipid carriers (Tf/HA-pDNA NLC) was constructed. Physicochemical properties such as morphology, size, and ζ-potential as well as release properties were evaluated. The in vitro and in vivo gene transfection efficiency of Tf/HA-pDNA NLC was evaluated in lung adenocarcinoma A549 cells and lung cancer bearing animal models. Tf/HA-pDNA NLC displayed significantly higher transfection efficiency than undecorated DNA-NLCs and single ligand-decorated NLCs in vitro and in vivo. The newly constructed NLCs could successfully load gene; and Tf and HA functioned as excellent targeting ligands to improve the cell targeting ability of the gene-loaded nanocarriers. The resulting dual ligands decorated vectors could be a promising targeted gene delivery system for the lung cancer treatment.
authors.affiliation: Department of Oncology, Shandong Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Experimental Pathology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Yueying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Public Health, Shandong Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000628:therapy; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014168:Transferrin / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D010714:Phosphatidylethanolamines; D012333:RNA, Messenger; D014168:Transferrin; C485184:enhanced green fluorescent protein; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid; D004247:DNA