Construction of smart inorganic nanoparticle-based ultrasound contrast agents and their biomedical applications

Ultrasound (US) imaging in combination with US contrast agents (UCAs) is a powerful tool in the modern biomedical field because of its high spatial resolution, easy access to patients and minimum invasiveness. The microbubble-based UCAs have been widely used in clinical diagnosis; however, they are only limited to the blood pool imaging and not applicable to the tissue-penetrated imaging due to their large particle size and structural instability. Inorganic nanoparticles (NPs), such as silica, gold and Fe_xO_y, featured with both satisfactory echogenic properties and structural stability have the potential to be used as a new generation of UCAs. In this review, we present the most recent progresses in the tailored construction of inorganic UCAs and their biomedical applications in the US imaging-involved fields. Firstly, the typical inorganic NPs with different structures including solid, hollow and multiple-layer forms will be comprehensively introduced in terms of their structure design, physicochemical property, US imaging mechanism and diverse applications; secondly, the recent progress in exploring the gas-generating inorganic NP system for US imaging purpose will be reviewed, and these intelligent UCAs are multifunctional for simultaneous US imaging and disease therapy; thirdly, several nanocomposite platforms newly constructed by combining inorganic UCAs with other functional components will be presented and discussed. These multifunctional NPs are capable of further enhancing the imaging resolution by providing more comprehensive anatomical information simultaneously. Last but not the least, the design criteria for developing promising UCAs to satisfy both clinical demands and optimized US imaging capability will be discussed and summarized in this review.