Nano Air Seeds Trapped in Mesoporous Janus Nanoparticles Facilitate Cavitation and Enhance Ultrasound Imaging

The current contrast agents utilized in ultrasound (US) imaging are based on microbubbles which suffer from a short lifetime in systemic circulation. The present study introduces a new type of contrast agent for US imaging based on bioresorbable Janus nanoparticles (NPs) that are able to generate microbubbles in situ under US radiation for extended time. The Janus NPs are based on porous silicon (PSi) that was modified via a nanostopper technique. The technique was exploited to prepare PSi NPs which had hydrophobic pore walls (inner face), while the external surfaces of the NPs (outer face) were hydrophilic. As a consequence, when dispersed in an aqueous solution, the Janus NPs contained a substantial amount of air trapped in their nanopores. The specific experimental setup was developed to prove that these nano air seeds were indeed acting as nuclei for microbubble growth during US radiation. Using the setup, the cavitation thresholds of the Janus NPs were compared to their completely hydrophilic counterparts by detecting the subharmonic signals from the microbubbles. These experiments and the numerical simulations of the bubble dynamics demonstrated that the Janus NPs generated microbubbles with a radii of 1.1 μm. Furthermore, the microbubbles generated by the NPs were detected with a conventional medical ultrasound imaging device. Long systemic circulation time was ensured by grafting the NPs with two different PEG polymers, which did not affect adversely the microbubble generation. The present findings represent an important landmark in the development of ultrasound contrast agents which possess the properties for both diagnostics and therapy.