Microbubble-mediated ultrasonic techniques for improved chemotherapeutic delivery in cancer.
Microbubble-mediated ultrasonic techniques for improved chemotherapeutic delivery in cancer.
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DOI：
10.3109/1061186x.2011.622397
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发表时间：
2012-01
影响因子：
4.5
通讯作者：
Hoyt K
中科院分区：
文献类型：
--
作者：
Sorace AG;Warram JM;Umphrey H;Hoyt K
超声（US）暴露的微泡（MB）造影剂能够暂时增强细胞膜的通透性。在癌症治疗中使用这种技术通过被动、局部递送来提高化疗的效率已成为一个新兴的研究领域。研究 US 参数对 MB 介导的癌症药物输送的影响。 2LMP乳腺癌细胞用于体外实验，2LMP荷瘤小鼠用于体内实验。研究了 MB 介导的 US 治疗参数（即频率、机械指数、脉冲重复周期、US 持续时间以及 MB 剂量和特性）对癌细胞的影响后膜通透性的变化。钙黄绿素（一种非渗透性荧光分子）和紫杉醇（化疗药物）用于评估膜渗透性。还通过组织学评估肿瘤反应。联合化疗和 MB 介导的 US 治疗（参数优化）比单独化疗增加了 50% 的癌细胞死亡。化疗药物的细胞摄取增加取决于美国系统参数。优化的 MB 介导的 US 疗法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，这可能会导致化疗药物剂量和全身毒性的降低。
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. Investigation of the influence of US parameters on MB mediated drug delivery in cancer. 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. Combination chemotherapy and MB-mediated US therapy with optimized parameters increased cancer cell death by 50% over chemotherapy alone. Increased cellular uptake of chemotherapeutic was dependent upon US system parameters. 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.