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Cavitation-facilitated transmembrane permeability enhancement induced by acoustically vaporized nanodroplets
Ultrasonics Sonochemistry ( IF 8.7 ) Pub Date : 2021-10-13 , DOI: 10.1016/j.ultsonch.2021.105790
Renjie Song 1 , Chunbing Zhang 2 , Fengmeng Teng 2 , Juan Tu 3 , Xiasheng Guo 1 , Zheng Fan 4 , Yinfei Zheng 5 , Dong Zhang 3
Affiliation  

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 × 108/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.



中文翻译:

由声学汽化纳米液滴诱导的空化促进跨膜渗透性增强

超声促进的跨膜通透性增强在中枢神经系统(CNS)疾病的治疗中引起了广泛的关注,它以一种更安全、更有效的方式将基因/药物输送到脑组织深部。尽管先前已经报道了使用声学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。在目前的研究中,使用硝酸纤维素 (NC) 膜来模拟 BBB 的多层孔结构。系统评价了不同浓度水平下相变纳米液滴的空化活性和穿透能力,并与 SonoVue 微泡获得的结果进行了比较。被动空化检测表明,汽化的纳米液滴比微泡产生的惯性空化 (IC) 活动强度较小但更持久。结果,具有足够高的浓度(~5×108 /mL),相变纳米液滴比微泡更有效地使荧光示踪剂(FITC,150 kDa)更深和更均匀地穿透NC膜,并且观察到累积IC剂量与量之间呈正相关的渗透 FITC。体内研究进一步证实,通过打开大鼠大脑中的 BBB,声学汽化纳米液滴的性能优于微泡。这些结果表明,相变纳米液滴可以作为一种安全、高效、耐用的试剂,在生物医学应用中实现令人满意的空化介导的渗透增强效果。

更新日期:2021-10-15
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