There is great interest in designing new medical imaging contrast agents that can permit multiple imaging and therapy applications using a single agent. This would provide concurrent contrast imaging for multiple modalities with complementary spatial, temporal and depth resolution for the more accurate diagnosis and local treatment of diseased tissue. Microbubbles (MBs) have long been used as effective contrast agents for ultrasound imaging in patients and have recently been explored as therapeutic agents in vivo. Here, we present a new strategy for the simple and robust incorporation of various medical nanoparticles (NPs) into monodisperse MBs based upon the controlled pH-based regulation of the electrostatic attraction between NPs and the MB shell. Using this simple approach, protein-coated, perfluorocarbon MBs (3-9 μm) were incorporated with various NPs including silica-coated quantum dots (QDs), gold nanorods (Au NRs), Fe_3O_4, and Gd-loaded silica NPs for optical, photoacoustic and MR imaging, respectively. This work reveals the potential of modular synthesis of a variety of NP- microbubble constructs to represent flexible, user-defined multifunctional imaging and therapy agents tailored for specific applications and disease types.
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