Controlled assembly of magnetic nanoparticles on microbubbles for multimodal imaging

Abstract

Magnetic microbubbles (MMBs) consisting of microbubbles (MBs) and magnetic nanoparticles (MNPs) were synthesized for use as novel markers for improving multifunctional biomedical imaging. The MMBs were fabricated by assembling MNPs in different concentrations on the surfaces of MBs. The relationships between the structure, magnetic properties, stability of the MMBs, and their use in magnetic resonance/ultrasound (MR/US) dual imaging applications were determined. The MNPs used were NPs of 3-aminopropyltriethoxysilane (APTS)-functionalized superparamagnetic iron oxide γ-Fe₂O₃ (SPIO). SPIO was assembled on the surfaces of polymer MBs using a “surface-coating” approach. An analysis of the underlying mechanism showed that the synergistic effects of covalent coupling, electrostatic adsorption, and aggregation of the MNPs allowed them to be unevenly assembled in large amounts on the surfaces of the MBs. With an increase in the MNP loading amount, the magnetic properties of the MMBs improved significantly; in this way, the shell structure and mechanical properties of the MMBs could be modified. For surface densities ranging from 2.45 × 10⁻⁷ μg per MMB to 8.45 × 10⁻⁷ μg per MMB, in vitro MR/US imaging experiments showed that, with an increase in the number of MNPs on the surfaces of the MBs, the MMBs exhibited better T₂ MR imaging contrast, as well as an increase in the US contrast for longer durations. In vivo experiments also showed that, by optimizing the structure of the MMBs, enhanced MR/US dual-modality image signals could be obtained for mouse tumors. Therefore, by adjusting the shell composition of MBs through the assembly of MNPs in different concentrations, MMBs with good magnetic and acoustic properties for MR/US dual-modality imaging contrast agents could be obtained.