微泡介导的超声技术提高癌症化疗药物递送。
Microbubble-mediated ultrasonic techniques for improved chemotherapeutic delivery in cancer.
机构信息
Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
出版信息
J Drug Target. 2012 Jan;20(1):43-54. doi: 10.3109/1061186X.2011.622397. Epub 2011 Oct 10.
BACKGROUND
Ultrasound (US) exposed microbubble (MB) contrast agents have the capability to transiently enhance cell membrane permeability. Using this technique in cancer treatment to increase the efficiency of chemotherapy through passive, localized delivery has been an emerging area of research.
PURPOSE
Investigation of the influence of US parameters on MB-mediated drug delivery in cancer.
METHODS
The 2LMP breast cancer cells were used for in vitro experiments and 2LMP tumor-bearing mice were used during in vivo experiments. Changes in membrane permeability were investigated after the influence of MB-mediated US therapy parameters (i.e. frequency, mechanical index, pulse repetition period, US duration, and MB dosing and characteristics) on cancer cells. Calcein, a non-permeable fluorescent molecule, and Taxol, chemotherapeutic, were used to evaluate membrane permeability. Tumor response was also assessed histologically.
RESULTS
Combination chemotherapy and MB-mediated US therapy with optimized parameters increased cancer cell death by 50% over chemotherapy alone.
DISCUSSION
Increased cellular uptake of chemotherapeutic was dependent upon US system parameters.
CONCLUSION
Optimized MB-mediated US therapy has the potential to improve cancer patient response to therapy via increased localized drug uptake, which may lead to a lowering of chemotherapeutic drug dosages and systemic toxicity.
背景
超声（US）暴露的微泡（MB）对比剂具有瞬时增强细胞膜通透性的能力。将该技术应用于癌症治疗中，通过被动、局部递送来提高化疗效率，是一个新兴的研究领域。
目的
研究超声参数对 MB 介导的癌症药物传递的影响。
方法
在体外实验中使用 2LMP 乳腺癌细胞，在体内实验中使用 2LMP 荷瘤小鼠。研究了 MB 介导的 US 治疗参数（频率、机械指数、脉冲重复周期、US 持续时间、MB 剂量和特性）对癌细胞的影响后，细胞膜通透性的变化。使用非通透性荧光分子 calcein 和化疗药物 Taxol 评估膜通透性。还进行了组织学评估肿瘤反应。
结果
联合化疗和 MB 介导的 US 治疗与优化参数相比，单独化疗使癌细胞死亡增加了 50%。
讨论
细胞摄取化疗药物的增加取决于 US 系统参数。
结论
优化的 MB 介导的 US 治疗有可能通过增加局部药物摄取来改善癌症患者对治疗的反应，从而可能降低化疗药物剂量和全身毒性。
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