Ultrasound-induced mild hyperthermia improves the anticancer efficacy of both Taxol® and paclitaxel-loaded nanocapsules
Ultrasound-induced mild hyperthermia improves the anticancer efficacy of both Taxol® and paclitaxel-loaded nanocapsules
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DOI：
10.1016/j.jconrel.2017.08.041
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发表时间：
2017-10-28
影响因子：
10.8
通讯作者：
Tsapis, Nicolas
中科院分区：
文献类型：
--
作者：
Boissenot, Tanguy;Bordat, Alexandre;Tsapis, Nicolas
我们在体外和体内研究了超声对紫杉醇纳米胶囊的影响。这些纳米胶囊具有聚（DL-丙交酯-共-乙交酯）-聚（乙二醇）（PLGA-PEG）的外壳和全氟辛基溴（PFOB）的液体核心。体外实验表明，由于纳米胶囊的尺寸小，外壳厚而坚硬，因此机械效应（如空化）可以忽略不计。由于机械效应不能增加紫杉醇的递送，我们在体内研究中关注超声的热效应。因此，在磁共振成像引导下，在体内优化聚焦超声序列，以获得具有高声压的局部轻度热疗。然后在皮下CT-26结肠癌小鼠模型中体内测试超声诱导的轻度高温（41-43摄氏度）。当应用热疗时，已经观察到负载紫杉醇的纳米胶囊和紫杉醇的商业制剂即Taxol（R）对肿瘤生长的抑制（p < 0.05）。在高声压下超声诱导的轻度热疗似乎是一种有趣的策略，以提高局部细胞毒性的疗效。
We study the influence of ultrasound on paclitaxel-loaded nanocapsules in vitro and in vivo. These nanocapsules possess a shell of poly(DL-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) and a liquid core of perfluorooctyl bromide (PFOB). In vitro experiments show that mechanical effects such as cavitation are negligible for nanocapsules due to their small size and thick and rigid shell. As the mechanical effects were unable to increase paclitaxel delivery, we focused on the thermal effects of ultrasound in the in vivo studies. A focused ultrasound sequence was therefore optimized in vivo under magnetic resonance imaging guidance to obtain localized mild hyperthermia with high acoustic pressure. Ultrasound-induced mild hyperthermia (41-43 degrees C) was then tested in vivo in a subcutaneous CT-26 colon cancer murine model. As hyperthermia is applied, an inhibition of tumor growth for both paclitaxel-loaded nanocapsules and the commercial formulation of paclitaxel, namely Taxol (R) have been observed (p < 0.05). Ultrasound-induced mild hyperthermia at high acoustic pressure appears as an interesting strategy to enhance cytotoxic efficacy locally.