Nonspherical ultrasound microbubbles.
Nonspherical ultrasound microbubbles.
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DOI：
10.1073/pnas.2218847120
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发表时间：
2023-03-28
影响因子：
11.1
通讯作者：
Lammers, Twan
中科院分区：
文献类型：
--
作者：
Dasgupta, Anshuman;Sun, Tao;Palomba, Roberto;Rama, Elena;Zhang, Yongzhi;Power, Chanikarn;Moeckel, Diana;Liu, Mengjiao;Sarode, Apoorva;Weiler, Marek;Motta, Alessandro;Porte, Celine;Magnuska, Zuzanna;Elshafei, Asmaa Said;Barmin, Roman;Graham, Adam;McClelland, Arthur;Rommel, Dirk;Stickeler, Elmar;Kiessling, Fabian;Pallares, Roger M.;De Laporte, Laura;Decuzzi, Paolo;McDannold, Nathan;Mitragotri, Samir;Lammers, Twan
微泡（MB）广泛应用于超声（US）成像和超声介导的药物递送。到目前为止，仅使用了球形微泡，这可能是因为表面张力从热力学角度迫使充气泡始终呈完美的球形。在此，我们表明，通过对基于聚氰基丙烯酸丁酯的聚合物微泡施加热能和机械能进行一维拉伸，有可能生成非球形微泡。研究发现，非球形微泡在小鼠静脉注射后，会更靠近血管壁，且在体内具有更长的循环时间。正因如此，与经颅聚焦超声结合使用时，非球形微泡在暂时打开血脑屏障方面的表现优于球形微泡。这些发现为设计用于超声介导药物递送的非球形聚合物基微泡开辟了道路。
表面张力赋予微泡（MB）完美的球形。在此，我们证明微泡可以被设计成非球形，赋予它们用于生物医学应用的独特特性。通过在高于其玻璃化转变温度的条件下对球形聚氰基丙烯酸丁酯微泡进行一维拉伸，生成了各向异性微泡。与球形微泡相比，非球形聚合物微泡在多个方面表现更优，包括：i）在类似血管的流动小室中边缘聚集行为增强；ii）体外巨噬细胞摄取减少；iii）体内循环时间延长；iv）与经颅聚焦超声（FUS）结合时，体内血脑屏障（BBB）通透性增强。我们的研究确定了形状是微泡领域的一个设计参数，并为进一步探索各向异性微泡在超声增强药物递送和成像应用中的应用提供了合理且可靠的框架。
Microbubbles (MB) are widely used for ultrasound (US) imaging and US-mediated drug delivery. Thus far, only spherical MB have been employed, likely because surface tension thermodynamically forces air-filled bubbles to always exist in a perfect spherical shape. Here, we show that it is possible to generate nonspherical MB, applying thermal and mechanical energy to one-dimensionally stretch poly(butyl cyanoacrylate)–based polymeric MB. Nonspherical MB were found to move closer to blood vessel walls and have longer circulation times in vivo upon i.v. administration in mice. Because of this, upon combination with transcranial focused ultrasound, nonspherical MB outperformed spherical MB in temporarily permeabilizing the blood–brain barrier. These findings open up avenues for engineering nonspherical polymer-based MB for ultrasound-mediated drug delivery. Surface tension provides microbubbles (MB) with a perfect spherical shape. Here, we demonstrate that MB can be engineered to be nonspherical, endowing them with unique features for biomedical applications. Anisotropic MB were generated via one-dimensionally stretching spherical poly(butyl cyanoacrylate) MB above their glass transition temperature. Compared to their spherical counterparts, nonspherical polymeric MB displayed superior performance in multiple ways, including i) increased margination behavior in blood vessel–like flow chambers, ii) reduced macrophage uptake in vitro, iii) prolonged circulation time in vivo, and iv) enhanced blood–brain barrier (BBB) permeation in vivo upon combination with transcranial focused ultrasound (FUS). Our studies identify shape as a design parameter in the MB landscape, and they provide a rational and robust framework for further exploring the application of anisotropic MB for ultrasound-enhanced drug delivery and imaging applications.
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影响因子：
4.9
作者：
Liu M;Dasgupta A;Koczera P;Schipper S;Rommel D;Shi Y;Kiessling F;Lammers T
通讯作者：
Lammers T
影响因子：
3.5
作者：
Lee, Sei-Young;Ferrari, Mauro;Decuzzi, Paolo
通讯作者：
Decuzzi, Paolo
影响因子：
10.8
作者：
Koczera, Patrick;Appold, Lia;Lammers, Twan
通讯作者：
Lammers, Twan
影响因子：
1.2
作者：
Di Lascio, Nicole;Kusmic, Claudia;Faita, Francesco
通讯作者：
Faita, Francesco
影响因子：
2.8
作者：
Manneschi, C.;Pereira, R. C.;Decuzzi, P.
通讯作者：
Decuzzi, P.