超声空化增强体外视网膜母细胞瘤细胞的化疗效果。
Sonoporation enhances chemotherapeutic efficacy in retinoblastoma cells in vitro.
机构信息
Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
出版信息
Invest Ophthalmol Vis Sci. 2011 Jun 1;52(6):3868-73. doi: 10.1167/iovs.10-6501.
PURPOSE
To study the ability of ultrasound (US) and microbubbles (MB) to enhance chemotherapeutic efficacy against retinoblastoma Y79 cells in vitro.
METHODS
The experiment was performed in three stages. The authors first compared cell viability of Y79 cells exposed to doxorubicin versus cells exposed to doxorubicin combined with low-intensity, low-frequency US + MB. They then evaluated enhanced cell permeability by studying the intensity of intracellular fluorescence in cells exposed to doxorubicin versus those exposed to doxorubicin with US + MB. Lastly they evaluated the morphologic characteristics of the cells by scanning electron microscopy (SEM) to identify the presence of pores.
RESULTS
The Y79 cells exposed to doxorubicin with US + MB showed a significant decrease in cell viability at 72 hours compared with those exposed to doxorubicin alone (P = 0.02). Cells also showed immediate increased permeability to doxorubicin with the addition of US + MB compared with doxorubicin alone, which continued to increase over 60 minutes. SEM did not demonstrate physical pores at the lowest US + MB intensity shown to enhance intracellular doxorubicin fluorescence.
CONCLUSIONS
US + MB facilitates the uptake of chemotherapy in retinoblastoma Y79 cells in vitro. This occurs in the absence of visible pores, suggesting a possible secondary mechanism for increased drug delivery. This experiment is the first step toward enhancing chemotherapy with sonoporation in the treatment of intraocular tumors. This technique may lead to more effective chemotherapy treatments with less collateral damage to ocular tissues and may allow reduced systemic dosage and systemic side effects.
目的
研究超声（US）和微泡（MB）增强体外视网膜母细胞瘤 Y79 细胞化学疗效的能力。
方法
实验分三个阶段进行。作者首先比较了单独使用阿霉素和阿霉素联合低强度、低频 US+MB 处理的 Y79 细胞的细胞活力。然后，通过研究暴露于阿霉素的细胞与暴露于 US+MB 的阿霉素的细胞的细胞内荧光强度来评估增强的细胞通透性。最后，通过扫描电子显微镜（SEM）评估细胞的形态特征，以确定是否存在孔。
结果
与单独使用阿霉素相比，联合使用 US+MB 的 Y79 细胞在 72 小时时显示出细胞活力明显下降（P=0.02）。与单独使用阿霉素相比，添加 US+MB 后细胞对阿霉素的通透性立即增加，并且在 60 分钟内持续增加。在显示增强细胞内阿霉素荧光的最低 US+MB 强度下，SEM 未显示物理孔。
结论
US+MB 促进了体外视网膜母细胞瘤 Y79 细胞对化疗药物的摄取。在没有可见孔的情况下发生这种情况，表明增加药物递送的可能存在的次要机制。这项实验是朝着用声孔术增强眼内肿瘤化疗的第一步。该技术可能会导致更有效的化疗治疗，对眼部组织的损伤更小，并且可能允许减少全身剂量和全身副作用。
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