Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
Commissariat à l'Energie Atomique (CEA), Institut d'Imagerie Biomédicale (I(2)BM), Neurospin, Saclay, France.
J Control Release. 2017 Oct 28;264:219-227. doi: 10.1016/j.jconrel.2017.08.041. Epub 2017 Sep 1.
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.
我们研究了超声对紫杉醇负载纳米胶囊的体外和体内影响。这些纳米胶囊具有聚（DL-丙交酯-co-乙交酯）-聚乙二醇（PLGA-PEG）外壳和全氟辛基溴（PFOB）液体核心。体外实验表明，由于纳米胶囊的尺寸小且外壳厚而硬，空化等机械效应可以忽略不计。由于机械效应无法增加紫杉醇的递送，我们在体内研究中专注于超声的热效应。因此，在磁共振成像引导下对体内聚焦超声序列进行了优化，以获得局部温和的高热疗和高声压。然后在皮下 CT-26 结肠癌小鼠模型中体内测试了超声诱导的温和热疗（41-43°C）。随着热疗的应用，观察到紫杉醇负载纳米胶囊和紫杉醇的商业制剂 Taxol®均抑制肿瘤生长（p<0.05）。高声压下的超声诱导温和热疗似乎是一种增强局部细胞毒性作用的有趣策略。
