Experimental study for development of microbubble applicable to clinical use in oral cancer chemotherapy

适用于口腔癌化疗临床的微泡研制实验研究

基本信息

批准号：
17592064
负责人：
MORIKAWA Hidehiro
金额：
$ 2.37万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

In the present study, we have developed a micro-imaging system using microbubbles as an effective type of ultrasound contrast agent, and a molecular delivery system for oral cancer therapy using microbubbles and ultrasound. As a result, it was clarified that microbubbles of 200nm in diameter, flowing blood vessels, could be visualized by using high-resolution ultrasound micro-imaging system (the highest frequency : 80MHz). In addition, when the nanosized bubbles less than a diameter of 200nm were used as an ultrasound contrast agent, the enhanced permeability and retention effect, that is the property by which the bubbles tend to accumulate in tumor tissue much more than they do in normal tissues, was also visualized by the ultrasound micro-imaging system. On the other hand, to test whether the combined use of microbubbles and ultrasound has a potential to deliver some therapeutic materials into cancer cells, we examined the delivery efficiency of 5-FU and cisplatin, and a suicide gene, herpes simplex virus thymidine kinase (HSVtk) gene. From results of in vitro and in vivo studies using cancer cell lines and experimental mice, microbubbles with ultrasound produced significant cytotoxicity not seen with either ultrasound or drug alone. Moreover, HSVtk gene transfection to cancer cells using microbubbles and ultrasound showed a potential of cytotoxic sensitivity by ganciclovir. These results suggests that simultaneous use of the micro-imaging system and the molecular delivery system by using the microbubbles and ultrasound method combined with anti-cancer agents and/or suicide gene therapy has a potential to treat oral cancer.

在本研究中，我们开发了一种使用微泡作为有效类型的超声造影剂的显微成像系统，以及使用微泡和超声治疗口腔癌的分子递送系统。结果表明，使用高分辨率超声波显微成像系统（最高频率：80MHz）可以可视化直径200nm的微泡、流动的血管。此外，当直径小于200nm的纳米级气泡用作超声造影剂时，增强的渗透性和滞留效应，即气泡在肿瘤组织中比在正常组织中更容易积聚的特性，也可以通过超声显微成像系统进行可视化。另一方面，为了测试微泡和超声波的联合使用是否有可能将一些治疗材料递送到癌细胞中，我们检查了 5-FU 和顺铂以及自杀基因单纯疱疹病毒胸苷激酶的递送效率。 HSVtk) 基因。根据使用癌细胞系和实验小鼠进行的体外和体内研究的结果，超声波微泡产生了显着的细胞毒性，这是单独使用超声波或药物所未见的。此外，使用微泡和超声波将 HSVtk 基因转染到癌细胞中，显示出更昔洛韦具有潜在的细胞毒性敏感性。这些结果表明，通过使用微泡和超声方法同时使用显微成像系统和分子递送系统，结合抗癌剂和/或自杀基因疗法，具有治疗口腔癌的潜力。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A non-invasive tissue-specific molecular delivery method of cancer gene therapy.

癌症基因治疗的非侵入性组织特异性分子递送方法。

DOI：
发表时间：
2006
期刊：
Minim Invasive Ther Allied Techol 15(4)
影响因子：
0
作者：
Tetsuya Kodama;Atsuko Aoi;Georges Vassaux Shiro Mori;Hidehiro Morikawa;Kenichiro Koshiyama;Takeru Yano;Shigeo Fujikawa;Yukio Tomita
通讯作者：
Yukio Tomita