title: Antitumoral efficacy by systemic delivery of heparin conjugated polyethylenimine-plasmid interleukin-15 complexes in murine models of lung metastasis.
abstract: Gene therapy shows promising application in cancer therapy, but the lack of an ideal gene delivery system is still a tough challenge for cancer gene therapy. Previously, we prepared a novel cationic nanogel, heparin-polyethylenimine (HPEI), which had potential application in gene delivery. In the present study, we constructed a plasmid with high expression efficiency of interleukin-15 (IL15) and investigated the effects HPEI-plasmid IL15 (HPEI-pIL15) complexes on the distribution level of the lung. We then evaluated the anticancer effect of HPEI-pIL15 complexes on lung metastases of B16-F10 melanoma and CT26 colon carcinoma. These results demonstrated that intravenous injection of the HPEI-pIL15 complex exhibited the highest plasmid distribution level in the lung compared with that of PEI2K-pIL15 and PEI25K-pIL15, and mice treated with HPEI-pIL15 had a lower tumor metastasis index compared with other treatment groups. Moreover, the number of natural killer cells, which were intermingled among the tumor cells, and the level of tumor necrosis factor-α and interferon-γ in the serum also increased in the pIL15-treated mice. Furthermore, the cytotoxic activity of spleen cells also increased significantly in the HPEI-pIL15 group. In addition, induction of apoptosis and inhibition of cell proliferation in lung tumor foci in the HPEI-pIL15 group was observed. Taken together, treating lung metastasis cancer with the HPEI nanogels delivered by plasmid IL15 might be a new and interesting cancer gene therapy protocol.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xikun
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Li
authors.forename: Maling
authors.initials: M
authors.lastname: Gou
authors.forename: Ji
authors.initials: J
authors.lastname: Qiu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Chuanjiang
authors.initials: C
authors.lastname: Yu
authors.forename: Yinbin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.forename: Xiu
authors.initials: X
authors.lastname: Teng
authors.forename: Zhongwen
authors.initials: Z
authors.lastname: Chen
authors.forename: Can
authors.initials: C
authors.lastname: Luo
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Guobo
authors.initials: G
authors.lastname: Shen
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Qian
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006493:Heparin / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000096:biosynthesis; D019409:Interleukin-15 / Q000235:genetics*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000080385:Nanogels; D010957:Plasmids; D011092:Polyethylene Glycols; D011094:Polyethyleneimine / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D019409:Interleukin-15; D000080385:Nanogels; D014409:Tumor Necrosis Factor-alpha; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D007371:Interferon-gamma; D011094:Polyethyleneimine; D006493:Heparin