The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma.

脑疾病的治疗受到血脑屏障（BBB）的阻碍，该屏障可防止大多数药物进入大脑。具有微泡的聚焦超声（FUS）可以安全且可逆地打开血脑屏障。全身性药物注射可能会诱发毒性，但是将其封装到纳米颗粒中会减少正常组织中的积累。在这里，我们使用基于聚（2-乙基-丁基氰基丙烯酸酯）纳米粒子稳定的微气泡的新型平台，以在黑色素瘤脑转移模型中透化血脑屏障。借助在1.1 MHz和7.8 MHz处产生FUS的双频超声换能器，我们使用纳米颗粒微气泡和低频FUS打开了血脑屏障，然后应用高频FUS产生声辐射力并将纳米颗粒推过细胞外基质。使用共聚焦显微镜和图像分析，我们量化了脑实质中的纳米颗粒外渗和分布。我们还评估了出血以及P-糖蛋白（一种关键的BBB成分）的表达。FUS和微泡在脑实质中分布了纳米颗粒，其分布取决于BBB的开放程度。声辐射力的结果尚无定论，但在一些动物中可以检测到一些影响。超声处理后，P-糖蛋白没有明显改变。总之，具有我们的纳米颗粒稳定微泡的FUS可以实现脑实质中纳米颗粒的积累和置换。FUS和微泡在脑实质中分布了纳米颗粒，其分布取决于BBB的开放程度。声辐射力的结果尚无定论，但在一些动物中可以检测到一些影响。超声处理后，P-糖蛋白没有明显改变。总之，具有我们的纳米颗粒稳定微泡的FUS可以实现脑实质中纳米颗粒的积累和置换。FUS和微泡在脑实质中分布了纳米颗粒，其分布取决于BBB的开放程度。声辐射力的结果尚无定论，但在一些动物中，可以检测到一些影响。超声处理后，P-糖蛋白没有明显改变。总之，具有我们的纳米颗粒稳定微泡的FUS可以实现脑实质中纳米颗粒的积累和置换。