Multifunctional Ultrasound Contrast Agents Integrating Targeted Imaging and Therapy

Abstract

As the most routinely used ultrasound contrast agent (UCA), ultrasound-responsive microbubbles can be developed as a multifunctional platform by loading multiple functional components into their shells or core domains. Additionally, such microbubbles can be coupled with targeting ligands for selective contrasting of the areas of disease and be selectively destroyed in the ultrasound field. Therefore, multifunctional ultrasound contrast agents hold great promise for contrast enhancement, molecular imaging, multimodal imaging, and drug/gene delivery with the opportunity for rational therapeutic dosing, as well as integrated diagnostics and therapeutics. As a result, multifunctional UCAs are highly advantageous to (pre)clinical implementation, not only because they could help visualize drug distribution and drug release at the target site and understand various essential aspects of the drug delivery process but also because they could contribute to the optimization of strategies relying on triggered drug release, to the prediction and real-time monitoring of therapeutic responses, and hence to the development of more efficient and less toxic treatment regimens for individual patients. This current review describes a biomedical engineering design process in which state-of-the-art UCA platforms can be designed to synergize ultrasonic imaging with other noninvasive imaging modalities, as well as to integrate imaging (diagnosis) and therapy. Multimodality imaging based on UCAs may create an exciting clinical opportunity and flexibility unachievable with either modality alone. Multimodal molecular imaging-guided targeted drug delivery and therapy will likely change the future of clinical medicine as these technologies continue to mature.