Due to its safety, low cost, high tissue penetration depth, and real-time imaging capability, ultrasound imaging is widely used in the clinic. Ultrasound contrast agents (UCAs), such as lipid stabilized perfluorocarbon microbubbles, can greatly enhance the ultrasound signal and enable molecular imaging of the disease-related biomarkers. However, their large size and poor stability in the circulation limit their use in the vascular space. To expand the applications of molecular ultrasound imaging beyond vasculature, robust UCAs with sizes small enough for extravasation from circulation (&lt;200 nm) should be developed. One such promising candidate is the amphiphilic (e. g. lipids or amphiphilic polymers) coated hydrophobic mesoporous silica nanoparticles (MSNs). At their hydrophobic interfaces, such nanoparticles can stabilize gas-pockets, which can nucleate echogenic micrometer-sized bubbles under reduced acoustic pressures. In addition, their surfaces can be modified to improve their biocompatibility and for biomarker targeting. However, previously developed amphiphilic coated hydrophobic MSNs require high acoustic pressures to nucleate the echogenic bubbles. Thus, a high intensity focused ultrasound (HIFU) transducer is usually applied to provide such high acoustic pressures for contrast enhancement. The use of HIFU transducer not only complicates the ultrasound imaging instrumentation but also limits the imaging volume to the focal volume of the HIFU transducer (typically a few mm<sup>3</sup>). Here, we developed a method to prepare amphiphilic coated hydrophobic MSNs that can generate echogenic bubbles at relatively low acoustic pressures, which can be achieved by using conventional medical ultrasound instruments. Using this method, we prepared 50 nm UCAs that can enhance the contrast of B-mode ultrasound images, at mechanical indices (MI) as low as 0.7 (well below the FDA limit of 1.9), when dispersed in buffer solutions, serum, or tissue-mimicking gel phantoms at particle concentrations down to 10 µg/mL.<br/>

Surface engineering of mesoporous silica nanoparticles to create highly echogenic nanoscale ultrasound contrast agents

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.