Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule Aachen University, 52074 Aachen, Germany.
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2218847120. doi: 10.1073/pnas.2218847120. Epub 2023 Mar 20.
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.
表面张力使微泡（MB）呈现完美的球形。在这里，我们证明可以对 MB 进行工程设计，使它们变成非球形，从而为生物医学应用赋予它们独特的特性。各向异性 MB 是通过在玻璃化转变温度以上对球形聚氰基丙烯酸正丁酯 MB 进行一维拉伸而产生的。与它们的球形对应物相比，非球形聚合物 MB 在多个方面表现出优异的性能，包括 i）在类似血管的流动腔中增加了靠边行为，ii）体外减少了巨噬细胞摄取，iii）体内循环时间延长，以及 iv）与经颅聚焦超声（FUS）结合后增强血脑屏障（BBB）渗透。我们的研究确定了形状是 MB 领域中的一个设计参数，并为进一步探索各向异性 MB 在超声增强药物输送和成像应用中的应用提供了合理且强大的框架。
