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

作者：Kim Jung Seok; Kang Seong Jae; Jeong Hwa Yeon; Kim Min Woo; Park Sang Il; Lee Yeon Kyung; Kim Hong Sung; Kim Keun Sik; Park Yong Serk^*

来源：International Journal of Oncology, 2016, 49(3): 1130-1138.

DOI：10.3892/ijo.2016.3619

• cancer
• liposomes
• salmosin
• interleukin-12
• gene therapy

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.

• 出版日期2016-9