title: Targeted lung cancer therapy: preparation and optimization of transferrin-decorated nanostructured lipid carriers as novel nanomedicine for co-delivery of anticancer drugs and DNA.
abstract: OBJECTIVE
  Nanostructured lipid carriers (NLC) represent an improved generation of lipid nanoparticles. They have specific nanostructures to accommodate drugs/genes, and thus achieve higher loading capacity. The aim of this study was to develop transferrin (Tf)-decorated NLC as multifunctional nanomedicine for co-delivery of paclitaxel (PTX) and enhanced green fluorescence protein plasmid.
  
  
  METHODS
  Firstly, Tf-conjugated ligands were synthesized. Secondly, PTX- and DNA-loaded NLC (PTX-DNA-NLC) was prepared. Finally, Tf-containing ligands were used for the surface decoration of NLC. Their average size, zeta potential, drug, and gene loading were evaluated. Human non-small cell lung carcinoma cell line (NCl-H460 cells) was used for the testing of in vitro transfection efficiency, and in vivo transfection efficiency of NLC was evaluated on mice bearing NCl-H460 cells.
  
  
  RESULTS
  Tf-decorated PTX and DNA co-encapsulated NLC (Tf-PTX-DNA-NLC) were nano-sized particles with positive zeta potential. Tf-PTX-DNA-NLC displayed low cytotoxicity, high gene transfection efficiency, and enhanced antitumor activity in vitro and in vivo.
  
  
  CONCLUSIONS
  The results demonstrated that Tf-PTX-DNA-NLC can achieve impressive antitumor activity and gene transfection efficiency. Tf decoration also enhanced the active targeting ability of the carriers to NCl-H460 cells. The novel drug and gene delivery system offers a promising strategy for the treatment of lung cancer.
authors.affiliation: Department of Radiotherapy, Cancer Centre, Qilu Hospital, Shandong University, Ji'nan, Shandong, People's Republic of China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Affiliated Hospital of Northwest Institute of Mechanical and Electrical Engineering, Xianyang, Shaanxi, People's Republic of China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Radiotherapy, Cancer Centre, Qilu Hospital, Shandong University, Ji'nan, Shandong, People's Republic of China.
authors.forename: Bingxu
authors.initials: B
authors.lastname: Tan
authors.affiliation: Department of Radiotherapy, Cancer Centre, Qilu Hospital, Shandong University, Ji'nan, Shandong, People's Republic of China.
authors.forename: Shanghui
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of Radiotherapy, Cancer Centre, Qilu Hospital, Shandong University, Ji'nan, Shandong, People's Republic of China.
authors.forename: Zhulong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Radiotherapy, Cancer Centre, Qilu Hospital, Shandong University, Ji'nan, Shandong, People's Republic of China.
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Radiotherapy, Cancer Centre, Qilu Hospital, Shandong University, Ji'nan, Shandong, People's Republic of China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Thoracic Surgery, Qilu Hospital, Shandong University, Ji'nan, Shandong, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D050997:Nanomedicine / Q000379:methods*; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D014162:Transfection / Q000379:methods*; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D014168:Transferrin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004247:DNA; D017239:Paclitaxel
keywords: active targeting systems; co-delivery; nanostructured lipid carriers; paclitaxel; transferrin decoration