Phys Med Biol. 2013 Nov 21;58(22):8135-51. doi: 10.1088/0031-9155/58/22/8135.
Nanomedicine-based delivery with non-invasive techniques is a promising approach to increase local drug concentration and to reduce systemic side effects. Focused ultrasound (FUS) has become a promising strategy for non-invasive local drug delivery by mild hyperthermia. In this study, traditional temperature-sensitive liposomes (TTSLs) encapsulating doxorubicin (DOX) were evaluated for FUS-mediated drug delivery with an in-vitro FUS setup. In-vitro studies showed quantitative release of the DOX from the lumen of the temperature-sensitive liposomes when heated to 42 °C with FUS using 1 MHz sinusoidal waves at 1.75 MPa for 10 min. No release was observed when heated at 37 °C. Moreover, we showed that DOX released from TTSLs by FUS is as efficiently internalized by glioblastoma cells as free DOX at 37 °C. In-vitro therapeutic evaluation showed that exposure of a cell monolayer to FUS-activated TTSLs induced a 60% and a 50% decrease in cell viability compared to cell medium and to TTSLs preheated at 37 °C, respectively. Using an in-vitro 3D cell culture model, the results showed that after FUS-mediated hyperthermia, preheated liposomes induced a 1.7-fold decrease in U-87 MG spheroid growth in comparison to the preheated liposomes at 37 °C. In conclusion, our results show that in-vitro FUS allows the evaluation of TTSLs and does not modify the cellular uptake of the released DOX nor its cytotoxic activity.
基于纳米医学的递送技术与非侵入性技术相结合，是提高局部药物浓度和减少全身副作用的一种很有前途的方法。聚焦超声（FUS）已成为一种很有前途的非侵入性局部药物递送策略，通过温和的热疗来实现。在这项研究中，我们评估了传统的温度敏感脂质体（TTSLs）包载阿霉素（DOX），并用体外 FUS 装置进行 FUS 介导的药物递送。体外研究表明，当用 1 MHz 正弦波在 1.75 MPa 下加热至 42°C 10 分钟时，DOX 从温度敏感脂质体的腔中定量释放。当在 37°C 加热时，没有观察到释放。此外，我们表明，与 37°C 加热的 TTSLs 相比，由 FUS 从 TTSLs 释放的 DOX 被神经胶质瘤细胞有效内化，与游离 DOX 一样有效。体外治疗评估表明，与细胞培养基和在 37°C 预加热的 TTSLs 相比，将单层细胞暴露于 FUS 激活的 TTSLs 会分别导致细胞活力降低 60%和 50%。使用体外 3D 细胞培养模型，结果表明，与在 37°C 预加热的脂质体相比，FUS 介导的热疗后，预加热的脂质体可使 U-87 MG 球体生长减少 1.7 倍。总之，我们的结果表明，体外 FUS 可以评估 TTSLs，并且不会改变释放的 DOX 的细胞摄取或其细胞毒性活性。
