Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure
Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure
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DOI：
10.1016/j.jconrel.2009.10.027
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发表时间：
2010-03-03
影响因子：
10.8
通讯作者：
Maruyama, Kazuo
中科院分区：
文献类型：
--
作者：
Suzuki, Ryo;Namai, Eisuke;Maruyama, Kazuo
白细胞介素-12（IL-12）基因疗法有望有效对抗癌症，因为它可以启动免疫系统对抗癌细胞。在这种治疗中，重要的是诱导肿瘤组织中的IL-12基因表达。声致孔是一种有吸引力的技术，用于开发非侵入性和非病毒的基因递送系统，但由于基因递送效率低，仅使用超声的简单声致孔不是有效的癌症基因治疗。我们解决了这个问题，通过结合超声和新的超声敏感脂质体（气泡脂质体），其中包含超声成像气体全氟丙烷。我们以前的工作表明，这是一种有效的基因传递系统，并且气泡脂质体崩溃（空化）是由超声暴露引起的。在这项研究中，我们评估了该系统在使用IL-12编码质粒DNA的癌症基因治疗中的实用性。Bubble脂质体和超声的组合显著抑制了肿瘤生长。这种治疗作用是T细胞依赖性的，主要需要效应期的CD 8（+）T淋巴细胞，如小鼠体内耗竭试验所证实的。此外，在小鼠体内观察到CD 8（+）T细胞的迁移，表明Bubble脂质体和超声的组合是IL-12癌症基因治疗中的良好的非病毒载体系统。(C)2009 Elsevier B. V.保留所有权利。
Interleukin-12 (IL-12) gene therapy is expected to be effective against cancers because it primes the immune system for cancer cells. In this therapy, it is important to induce IL-12 gene expression in the tumor tissue. Sonoporation is an attractive technique for developing non-invasive and non-viral gene delivery systems, but simple sonoporation using only ultrasound is not an effective cancer gene therapy because of the low efficiency of gene delivery. We addressed this problem by combining ultrasound and novel ultrasound-sensitive liposomes (Bubble liposomes) which contain the ultrasound imaging gas perfluoropropane. Our previous work showed that this is an effective gene delivery system, and that Bubble liposome collapse (cavitation) is induced by ultrasound exposure. In this study, we assessed the utility of this system in cancer gene therapy using IL-12 corded plasmid DNA. The combination of Bubble liposomes and ultrasound dramatically suppressed tumor growth. This therapeutic effect was T-cell dependent, requiring mainly CD8(+) T lymphocytes in the effector phase, as confirmed by a mouse in vivo depletion assay. In addition, migration of CD8(+) T cells was observed in the mice, indicating that the combination of Bubble liposomes and ultrasound is a good non-viral vector system in IL-12 cancer gene therapy. (C) 2009 Elsevier B.V. All rights reserved.