title: Co-delivery of plasmid DNA and doxorubicin by solid lipid nanoparticles for lung cancer therapy.
abstract: The co-delivery of DNA and antitumor drugs has the potential to treat cancer. In this study, we aimed to develop surface-modified, co-encapsulated solid lipid nanoparticles (SLN) containing enhanced green fluorescence protein plasmid (pEGFP) and doxorubicin (DOX) in order to create a multifunctional delivery system that targets lung cancer cells, in an effort to improve the efficacy of cancer therapy. DOX- and pEGFP-loaded SLN were prepared separately and then mixed to form co-encapsulated SLN (SLN/DE). Transferrin (Tf)-containing ligands were used for the surface coating of the vectors. The in vitro transfection efficiency of the modified vectors was evaluated using a human alveolar adenocarcinoma cell line (A549 cells) and the in vivo transfection efficiency of the modified vectors was evaluated using mice bearing A549 tumors. The Tf-modified DOX and pEGFP co-encapsulated SLN (T-SLN/DE) had a particle size of 267 nm with a 42 mV surface charge. The in vitro cytotoxicity of T-SLN/DE was low (cell viability was between 80 and 100% compared with the controls). T-SLN/DE displayed a remarkable therapeutic effect both in drug delivery and gene therapy. In conclusion, our results demonstrate that the multifunctional delivery system can improve the efficacy of cancer therapy through the combination of gene therapy and chemotherapy. In addition, the coating of active targeting ligands can improve the efficacy of the carriers at targeting lung cancer cells. Thus, the novel gene and drug delivery system offers an effective strategy for lung cancer gene therapy.
authors.affiliation: Department of Respiratory Medicine, General Hospital of Ji'nan Command of Chinese PLA, Ji'nan, Shandong 250031, P.R. China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Respiratory Medicine, General Hospital of Ji'nan Command of Chinese PLA, Ji'nan, Shandong 250031, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, General Hospital of Ji'nan Command of Chinese PLA, Ji'nan, Shandong 250031, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, General Hospital of Ji'nan Command of Chinese PLA, Ji'nan, Shandong 250031, P.R. China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Hematology, General Hospital of Ji'nan Command of Chinese PLA, Ji'nan, Shandong 250031, P.R. China.
authors.forename: Fansheng
authors.initials: F
authors.lastname: Kong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010957:Plasmids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014168:Transferrin / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D010714:Phosphatidylethanolamines; D014168:Transferrin; D049452:Green Fluorescent Proteins; C483858:phosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin