Multifunctional hard-shelled microbubbles for differentiating imaging, cavitation and drug release by ultrasound

Abstract

Polymeric microbubbles bearing a hard shell exhibit prominent stability and tunable acoustical properties that serve the purposes of biomedical imaging and ultrasound (US)-triggered cavitations. It is of great significance to expand the utility scope of hard-shelled microbubbles with multifunctionality, which will dramatically enhance the efficiency and precision of disease-oriented treatments. To this end, the multifunctional hard-shelled microbubbles (PMBs) for US imaging and US-triggered stimuli-responsive cavitations have been synthesized via a one-step in situ polymerization. Varied parameters including US frequency, acoustical powers and pulse duration time have been screened to optimize the cavitation conditions. It was notable to observe that by use of PMBs, a US-triggered progress of imaging, stable and inertial cavitations could be easily differentiated with an elaborately modulated parameter, which gives a visualizable pathway for imaging, stimuli-responsive cavitation, drug transportation and release at each stage. Meanwhile, commercial US contrast agents (Sonovue and Xueruixin with lipid and protein shell materials) have been compared with PMBs in terms of their cavitation performances. These valuable findings imply a promising perspective to use these multifunctional microbubbles as a novel visualizable theranostic strategy against diseases.