Local delivery system of cytotoxic agents to tumors by focused sonoporation
Local delivery system of cytotoxic agents to tumors by focused sonoporation
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DOI：
10.1038/sj.cgt.7701026
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发表时间：
2007-04-01
影响因子：
6.4
通讯作者：
Nishihara, T.
中科院分区：
文献类型：
--
作者：
Iwanaga, K.;Tominaga, K.;Nishihara, T.
近年来，超声靶向微泡破坏已被应用于分子基因治疗中，并开发了一种新的有效的非病毒基因转移方法——“超声穿孔”。我们在体外和体内研究了超声波对人牙龈鳞癌细胞株Ca9-22生长的抑制作用。采用流式细胞术和体外赫斯特染色法研究博来霉素（BLM）的细胞毒性。我们发现通过声孔传递BLM对Ca9-22细胞具有细胞毒性作用。我们的体内实验结果显示，在4周的实验期间，低剂量BLM后超声处理的Ca9-22细胞移植裸KSN/slc小鼠肿瘤几乎消失。组织学分析显示，细胞毒作用主要是细胞凋亡。我们之前报道了来自放线菌的细胞致死膨胀毒素B (cdtB)，一种牙周病细菌，在体外负责细胞周期阻滞和凋亡。因此，我们采用超声法将表达cdtb的质粒转染到Ca9-22细胞中，并在体外和体内检测细胞活力。我们发现，在体外和体内观察到表达cdtb的质粒后，超声诱导的Ca9-22细胞和凋亡细胞的生长明显抑制。这些发现表明，局部使用细胞毒性药物与超声穿孔是一种有效的分子肿瘤治疗方法。癌症基因治疗（2007）14,354-363。doi: 10.1038 / sj.cgt。7701026;2007年2月2日在线发布。
Recently, ultrasound-targeting microbubble destruction has been employed in molecular gene therapy, and a new potent nonviral gene transfer method known as 'sonoporation' has been developed. We investigated the efficiency of sonoporation toward growth inhibition of human gingival squamous carcinoma cell line, Ca9-22, in vitro and in vivo. The cytotoxicity of bleomycin (BLM) was investigated using flow-cytometric analysis and Hoechst's staining in vitro assay systems. We found that the delivery of BLM by sonoporation induced cytotoxic effect toward Ca9-22 cells in vitro. Our in vivo results showed that tumors nearly disappeared in Ca9-22 cell-implanted nude KSN/slc mice treated with a low dose of BLM followed by sonoporation during the 4-week experimental period. Histological analysis revealed that the cytotoxic effect was mainly apoptosis. We previously reported that the cytolethal distending toxin B (cdtB) from Actinobacillus actinomycetemcomitans, a periodontopathic bacterium, is responsible for cell cycle arrest and apoptosis in vitro. Thus, we used sonoporation to transfect a cdtB-expressing plasmid into Ca9-22 cells and examined cell viability in vitro and in vivo. We found that an administration of cdtB-expressing plasmid followed by sonoporationinduced marked growth inhibition of Ca9-22 cells and apoptotic cells were also observed in vitro and in vivo. These findings suggest that local administration of cytotoxic agents with sonoporation is a useful method for molecular cancer therapy. Cancer Gene Therapy (2007) 14, 354-363. doi: 10.1038/sj.cgt. 7701026; published online 2 February 2007.