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Ultrasound-induced mild hyperthermia improves the anticancer efficacy of both Taxol® and paclitaxel-loaded nanocapsules
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2017-09-01 , DOI: 10.1016/j.jconrel.2017.08.041
Tanguy Boissenot , Alexandre Bordat , Benoît Larrat , Mariana Varna , Hélène Chacun , Angelo Paci , Vianney Poinsignon , Elias Fattal , Nicolas Tsapis

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 °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® have been observed (p < 0.05). Ultrasound-induced mild hyperthermia at high acoustic pressure appears as an interesting strategy to enhance cytotoxic efficacy locally.



中文翻译:

超声诱导的轻度高温可改善紫杉醇和紫杉醇纳米胶囊的抗癌功效

我们在体外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)的壳和全氟辛基溴化物(PFOB)的液体核。体外实验表明,由于纳米胶囊尺寸小,外壳厚且坚硬,因此诸如空化作用等机械作用可忽略不计。由于机械作用无法增加紫杉醇的递送,因此我们在体内研究中着重于超声的热作用。因此在体内优化聚焦超声序列在磁共振成像指导下获得高声压的局部温和热疗。然后在皮下CT-26结肠癌鼠科动物模型中体内测试超声诱导的轻度高温(41​​–43°C)。当应用高温疗法时,已观察到紫杉醇负载的纳米胶囊和紫杉醇的商业制剂,即Taxol®对肿瘤生长的抑制作用(p  <0.05)。超声在高声压下引起的轻度热疗似乎是提高局部细胞毒性功效的有趣策略。

更新日期:2017-09-01
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