Heat-inducible TNF-α gene therapy combined with hyperthermia using magnetic nanoparticles as a novel tumor-targeted therapy
Heat-inducible TNF-α gene therapy combined with hyperthermia using magnetic nanoparticles as a novel tumor-targeted therapy
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DOI：
10.1038/sj.cgt.7700357
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发表时间：
2001-09-01
影响因子：
6.4
通讯作者：
Kobayashi, T
中科院分区：
文献类型：
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作者：
Ito, A;Shinkai, M;Kobayashi, T
热诱导的治疗性基因表达对于基因治疗是高度期望的，以使副作用最小化。此外，如果基因表达是由热应激触发的，则热疗和基因治疗的联合治疗效果是可能的。我们结合TNF-α基因治疗驱动的应激诱导型启动子，gadd 153，与热疗使用磁铁矿阳离子脂质体（MCLs）。在裸小鼠中，MCL在交变磁场下加热时诱导大部分肿瘤区域的细胞死亡。与未加热的肿瘤相比，这种热应激还导致由gadd 153启动子驱动的TNF-α基因表达增加3倍。TNF-α基因表达还观察到在外周区域，其中过热效应不足以引起细胞死亡。联合治疗在30天内强烈抑制了裸鼠的肿瘤生长，这表明了癌症治疗的潜力。
Heat-induced therapeutic gene expression is highly desired for gene therapy to minimize side effects. Furthermore, if the gene expression is triggered by heat stress, combined therapeutic effects of hyperthermia and gene therapy may be possible. We combined TNF-alpha gene therapy driven by the stress-inducible promoter, gadd 153, with hyperthermia using magnetite cationic liposomes (MCLs). In nude mice, MCLs induced cell death throughout much of the tumor area on heating under an alternating magnetic field. This heat stress also resulted in a 3-fold increase in TNF-alpha gene expression driven by the gadd 153 promoter as compared with that of nonheated tumor. TNF-alpha gene expression was also observed in the peripheral area where the hyperthermic effect was not enough to cause cell death. The combined treatment strongly arrested tumor growth in nude mice over a 30-day period, suggesting potential for cancer treatment.