Drug-loaded nanoscale cavitation agents, called nanodroplets, are an attractive solution to enhance and localize drug delivery, offering increased stability and prolonged half-life in circulation compared to microbubbles. However, the spatial precision with which drug can be released and delivered into brain tissue from such agents has not been directly mapped. Decafluorobutane lipid-shell droplets (206 +/− 6 nm) were loaded with a fluorescent blood-brain barrier (BBB)-penetrating dye (Nile Blue) and vaporized with ultrasound (1.66 MHz, 10 ms pulse length, 1 Hz pulse repetition frequency), generating transient echogenic microbubbles and delivering the encapsulated dye. The distribution and intensity of released fluorophore was mapped in a tissue-mimicking phantom, and in the brain of rats (Sprague Dawley, N = 4, n = 16). The release and distribution of dye was found to be pressure-dependent (0.2–3.5 MPa) and to occur only above the vaporization threshold of the nanodroplets (1.5 +/− 0.25 MPa in vitro, 2.4 +/− 0.05 MPa in vivo). Dye delivery was achieved with sub-millimetre spatial precision, covering an area of 0.4 to 1.5 mm in diameter, determined by the sonication pressure. The distribution and intensity of dye released at depth in the brain followed the axial pressure profile of the ultrasound beam. Nile Blue (354 Da, LogP 2.7) was compared to Nile Red (318 Da, LogP 3.8) and Quantum Dots (CdSe/ZnS, 5 nm diameter) to visualize the role of molecule size and lipophilicity in crossing the intact BBB following triggered release. Acoustic emissions were shown to predict the successful delivery of the BBB-penetrating dye and the extent of the distribution, demonstrating the theranostic capabilities of nanoscale droplets to precisely localize drug delivery in the brain.

载药纳米级空化剂，称为纳米液滴，是增强和定位药物递送的有吸引力的解决方案，与微泡相比，在循环中提供更高的稳定性和更长的半衰期。然而，尚未直接绘制药物从此类药物释放并输送到脑组织的空间精度。十氟丁烷脂质壳液滴（206 +/- 6 nm）装有荧光血脑屏障（BBB）穿透染料（尼罗蓝）并用超声（1.66 MHz，10 ms脉冲长度，1 Hz脉冲重复频率）汽化)，产生瞬时回声微泡并提供封装的染料。释放的荧光团的分布和强度在组织模拟体模和大鼠大脑中进行了映射 (Sprague Dawley, N = 4，n  = 16）。发现染料的释放和分布与压力有关 (0.2–3.5 MPa) 并且仅在高于纳米液滴的汽化阈值时发生（体外1.5 +/- 0.25 MPa ，体内2.4 +/- 0.05 MPa ））。染料输送以亚毫米的空间精度实现，覆盖直径为 0.4 到 1.5 毫米的区域，由超声压力决定。在大脑深处释放的染料的分布和强度遵循超声波束的轴向压力分布。将尼罗河蓝（354 Da，LogP 2.7）与尼罗河红（318 Da，LogP 3.8）和量子点（CdSe/ZnS，5 nm 直径）进行比较，以可视化分子大小和亲脂性在触发释放后穿过完整 BBB 的作用. 声发射显示可预测 BBB 穿透染料的成功递送和分布范围，证明纳米级液滴的治疗诊断能力可精确定位大脑中的药物递送。