Institute of Medical Science and Technology, University of Dundee, Dundee, UK.
Adv Exp Med Biol. 2012;733:135-44. doi: 10.1007/978-94-007-2555-3_13.
Recently, ultrasonic drug release has been a focus of many research groups for stimuli responsive drug release. It has been demonstrated that a focused ultrasound (FUS) beam rapidly increases the temperature at the focused tissue area. One potential mechanism of drug targeting is to utilize the induced heat to release or increase penetration of chemotherapy to cancer cells. The efficiency of targeted drug delivery may increase by using FUS beam in conjugation with nano--encapsulated drug carriers.The aim of this study is to investigate the effect of heat and ultrasound on the cellular uptake and therapeutic efficacy of an anticancer drug using Magnetic Resonance Imaging guided Focused Ultrasound (MRgFUS).
Human KB cells (CCL-17 cells) were seeded into 96-well plates and heat treated at 37-55°C for 2-10 min. Cell viability was determined using the colorimetric MTT assay. The cells were also subjected to MRgFUS and the degree of cell viability was determined. These experiments were conducted using an ExAblate 2000 system (InSightec, Haifa, Israel) and a GE 1.5 T MRI system, software release 15.
We have observed a significant decrease in human KB cell viability due to heat (>41°C) in the presence of Doxorubicin (DOX), in comparison with DOX at normal culture temperature (37°C). The synergistic effect of heat with DOX may be explained by several mechanisms. One potential mechanism may be increased penetration of DOX to the cells during heating. In addition, we have shown that ultrasound induced cavitation causes cell necrosis. DISCUSSION AND FUTURE WORK: Further investigation is required to optimize the potential of MRgFUS to enhance cellular uptake of therapeutic agents. A novel delivery nano-vehicle developed by CapsuTech will be investigated with MRgFUS for its potential as a stimuli responsive delivery system.
最近，超声药物释放已成为许多研究小组关注的焦点，用于刺激响应药物释放。已经证明，聚焦超声（FUS）束可以迅速增加聚焦组织区域的温度。一种潜在的药物靶向机制是利用诱导的热量来释放或增加化疗药物对癌细胞的渗透。通过使用 FUS 束与纳米封装药物载体结合，可以提高靶向药物输送的效率。本研究的目的是研究热和超声对磁共振成像引导聚焦超声（MRgFUS）中使用的抗癌药物的细胞摄取和治疗效果的影响。
将人 KB 细胞（CCL-17 细胞）接种到 96 孔板中，在 37-55°C 下热疗 2-10 分钟。使用比色 MTT 测定法测定细胞活力。还对细胞进行了 MRgFUS 处理，并测定了细胞活力的程度。这些实验是使用 ExAblate 2000 系统（InSightec，海法，以色列）和 GE 1.5T MRI 系统，软件版本 15 进行的。
我们观察到，在存在阿霉素（DOX）的情况下，由于热（>41°C），人 KB 细胞活力显着下降，与正常培养温度（37°C）下的 DOX 相比。热与 DOX 的协同作用可能通过几种机制来解释。一种潜在的机制可能是在加热过程中增加了 DOX 向细胞的渗透。此外，我们已经表明，超声诱导的空化会导致细胞坏死。
需要进一步研究以优化 MRgFUS 增强治疗剂细胞摄取的潜力。CapsuTech 开发的新型输送纳米载体将与 MRgFUS 一起进行研究，以评估其作为刺激响应输送系统的潜力。
