Anti-EGFR immunonanoparticles containing IL12 and salmosin genes for targeted cancer gene therapy

被引:8
作者
Kim, Jung Seok [1 ]
Kang, Seong Jae [1 ]
Jeong, Hwa Yeon [1 ]
Kim, Min Woo [1 ]
Park, Sang Il [1 ]
Lee, Yeon Kyung [1 ]
Kim, Hong Sung [2 ]
Kim, Keun Sik [3 ]
Park, Yong Serk [1 ]
机构
[1] Yonsei Univ, Dept Biomed Lab Sci, Wonju 220710, Gangwon, South Korea
[2] Korea Nazarene Univ, Dept Biomed Lab Sci, Cheonan, South Korea
[3] Konyang Univ, Dept Biomed Lab Sci, Daejeon, South Korea
基金
新加坡国家研究基金会;
关键词
cancer; liposomes; salmosin; interleukin-12; gene therapy; IN-VIVO; CATIONIC LIPIDS; DELIVERY; NANOPARTICLES; LIPOSOME; TRANSFECTION; PROGRESSION; DNA; INHIBITION; SAXATILIN;
D O I
10.3892/ijo.2016.3619
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1130 / 1138
页数:9
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