Inhibition of melanoma by ultrasound-microbubble-aided drug delivery suggests membrane permeabilization
Inhibition of melanoma by ultrasound-microbubble-aided drug delivery suggests membrane permeabilization
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DOI：
10.4161/cbt.6.8.4485
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发表时间：
2007-05
影响因子：
3.6
通讯作者：
S. Sonoda;K. Tachibana;E. Uchino;Toshifumi Yamashita;K. Sakoda;K. Sonoda;T. Hisatomi;Y. Izumi
中科院分区：
文献类型：
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作者：
S. Sonoda;K. Tachibana;E. Uchino;Toshifumi Yamashita;K. Sakoda;K. Sonoda;T. Hisatomi;Y. Izumi
超声造影诱导的空化已被证明可以增强细胞膜的通透性，从而促进有效的药物递送到细胞中，这是一种在微泡（MB）存在下可以增强的技术。在这里，我们采用这种方法作为治疗眼睑恶性黑色素瘤。恶性黑色素瘤在眼科发病率较高，但治疗较为困难。使用超声波和MB与抗癌药物博来霉素的组合比将更浓缩剂量的博来霉素单独应用于细胞培养物时实现了更大的B-16黑素瘤细胞的体外生长抑制。此外，在通过将B-16黑色素瘤细胞注射到SCID小鼠的下眼睑中而产生的体内肿瘤模型中，这种效果得到增强。当治疗与超声结合使用时，在较低剂量（0.5 mg/ml）下观察到博来霉素的抗肿瘤作用。当包括MB时，效果进一步增强，在0.06 mg/ml的博来霉素水平下发生肿瘤收缩。这些结果表明，超声和MB促进细胞有效的博来霉素摄取，并且该技术是一种潜在有用的药物递送方法。
Ultrasound exposure-induced cavitation has been shown to accentuate cell membrane permeability, thus promoting effective drug delivery into cells, a technique that can be enhanced in the presence of microbubbles (MB). Here we applied this method as a treatment for malignant melanoma of the eyelid. The incidence of malignant melanoma in ophthalmology is relatively high, but its treatment is cosmetically difficult. A greater in vitro growth suppression of B-16 melanoma cells was achieved using ultrasound and MB in combination with the anticancer drug bleomycin than when a more concentrated dose of bleomycin alone was applied to the cell culture. Moreover, this effect was enhanced in an in vivo tumor model created by injecting B-16 melanoma cells into the lower eyelids of SCID mice. The antitumor effect of bleomycin was observed at a lower dose (0.5 mg/ml) when the treatment was used in conjunction with ultrasound. The effect was further enhanced when MB were included, with tumor shrinkage occurring at bleomycin levels of 0.06 mg/ml. These results show that ultrasound and MB promote efficient bleomycin uptake by cells, and that the technique is a potentially useful drug delivery method.