title: Anti-EGFR immunonanoparticles containing IL12 and salmosin genes for targeted cancer gene therapy.
abstract: Tumor-directed gene delivery is of major interest in the field of cancer gene therapy. Varied functionalizations of non-viral vectors have been suggested to enhance tumor targetability. In the present study, we prepared two different types of anti-EGF receptor (EGFR) immunonanoparticles containing pDNA, neutrally charged liposomes and cationic lipoplexes, for tumor-directed transfection of cancer therapeutic genes. Even though both anti-EGFR immunonanoparticles had a high binding affinity to the EGFR-positive cancer cells, the anti-EGFR immunolipoplex formulation exhibited approximately 100-fold higher transfection to the target cells than anti-EGFR immunoliposomes. The lipoplex formulation also showed a higher transfection to SK-OV-3 tumor xenografts in mice. Thus, IL12 and/or salmosin genes were loaded in the anti-EGFR immunolipoplexes and intravenously administered to mice carrying SK-OV-3 tumors. Co-transfection of IL12 and salmosin genes using anti-EGFR immunolipoplexes significantly reduced tumor growth and pulmonary metastasis. Furthermore, combinatorial treatment with doxorubicin synergistically inhibited tumor growth. These results suggest that anti-EGFR immunolipoplexes containing pDNA encoding therapeutic genes could be utilized as a gene-transfer modality for cancer gene therapy.
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: Jung Seok
authors: JS
authors: Kim
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: Seong Jae
authors: SJ
authors: Kang
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: Hwa Yeon
authors: HY
authors: Jeong
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: Min Woo
authors: MW
authors: Kim
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: Sang Il
authors: SI
authors: Park
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: Yeon Kyung
authors: YK
authors: Lee
authors: Department of Biomedical Laboratory Science, Korea Nazarene University, Cheonan, Republic of Korea.
authors: Hong Sung
authors: HS
authors: Kim
authors: Department of Biomedical Laboratory Science, Konyang University, Daejeon, Republic of Korea.
authors: Keun Sik
authors: KS
authors: Kim
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: Yong Serk
authors: YS
authors: Park
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000008:administration & dosage* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003435:Crotalid Venoms / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage*; D018664:Interleukin-12 / Q000235:genetics*; D008081:Liposomes / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D061986:MCF-7 Cells; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D058726:Nanoconjugates / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D003435:Crotalid Venoms; D018796:Immunoconjugates; D008081:Liposomes; D058726:Nanoconjugates; C115393:salmosin; D018664:Interleukin-12; D000068818:Cetuximab