Key Laboratory of Modern Acoustics (MOE), Department of Physics, Collaborative Innovation Center of Advanced Microstructure, Nanjing University, Nanjing 210093, China.
Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210023, China.
Ultrason Sonochem. 2021 Nov;79:105790. doi: 10.1016/j.ultsonch.2021.105790. Epub 2021 Oct 13.
Ultrasound-facilitated transmembrane permeability enhancement has attracted broad attention in the treatment of central nervous system (CNS) diseases, by delivering gene/drugs into the deep site of brain tissues with a safer and more effective way. Although the feasibility of using acoustically vaporized nanodroplets to open the blood-brain-barrier (BBB) has previously been reported, the relevant physical mechanisms and impact factors are not well known. In the current study, a nitrocellulose (NC) membrane was used to mimic the multi-layered pore structure of BBB. The cavitation activity and the penetration ability of phase-changed nanodroplets were systemically evaluated at different concentration levels, and compared with the results obtained for SonoVue microbubbles. Passive cavitation detection showed that less intensified but more sustained inertial cavitation (IC) activity would be generated by vaporized nanodroplets than microbubbles. As the results, with a sufficiently high concentration (∼5 × 10/mL), phase-changed nanodroplets were more effective than microbubbles in enabling a fluorescent tracer agent (FITC, 150 kDa) to penetrate deeper and more homogeneously through the NC membrane, and a positive correlation was observed between accumulated IC dose and the amount of penetrated FITC. In vivo studies further confirmed acoustically vaporized nanodroplets performed better than microbubbles by opening the BBB in rats' brains. These results indicated that phase-changed nanodroplets can be used as a safe, efficient and durable agent to achieve satisfactory cavitation-mediated permeability enhancement effect in biomedical applications.
超声辅助跨膜通透性增强技术通过以更安全、更有效的方式将基因/药物递送到脑组织的深部部位，在治疗中枢神经系统（CNS）疾病方面引起了广泛关注。尽管先前已经报道了使用超声空化汽化纳米液滴打开血脑屏障（BBB）的可行性，但相关的物理机制和影响因素尚不清楚。在当前的研究中，使用硝酸纤维素（NC）膜模拟 BBB 的多层孔结构。系统评估了不同浓度水平下相变型纳米液滴的空化活性和穿透能力，并将其与 SonoVue 微泡的结果进行了比较。被动空化检测表明，汽化纳米液滴产生的惯性空化（IC）活性虽然强度较低，但持续时间更长。结果表明，在足够高的浓度（约 5×10/mL）下，与微泡相比，相变型纳米液滴更有效地使荧光示踪剂（FITC，150 kDa）穿透 NC 膜更深且更均匀，并且积累的 IC 剂量与穿透的 FITC 量之间存在正相关关系。体内研究进一步证实，在大鼠大脑中，超声空化汽化纳米液滴比微泡更有效地打开 BBB。这些结果表明，相变型纳米液滴可用作安全、高效和持久的试剂，以在生物医学应用中实现令人满意的空化介导的通透性增强效果。
