Nonspherical Ultrasound Microbubbles
Bioengineering Assistant Professor Tao Sun recently published his postdoctoral research from John A. Paulson School of Engineering and Applied Sciences and Brigham and Women’s Hospital on “Nonspherical ultrasound microbubbles,” in PNAS.
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 intravenous administration in mice. Combined 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 US-mediated drug delivery.
Abstract
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.