Nonspherical ultrasound microbubbles
Anshuman Dasgupta, Tao Sun, Roberto Palomba, Elena Rama, Yongzhi Zhang, Chanikarn Power, Diana Moeckel, Mengjiao Liu, Apoorva Sarode, Marek Weiler, Alessandro Motta, Céline Porte, Zuzanna Magnuska, Asmaa Said Elshafei, Roman A. Barmin, Adam Graham, Arthur McClelland, Dirk Rommel, Elmar Stickeler, Fabian Kießling, Roger M. Pallares, Laura De Laporte, Paolo Decuzzi, Nathan McDannold, Samir Mitragotri, Twan Lammers
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.