Superparamagnetic iron oxide and drug complex-embedded acoustic droplets for ultrasound targeted theranosis

Ultrasound-triggered acoustic droplet vaporization (ADV) has been reported as a mechanical and chemical theranostic strategy for tumor treatment. However, targeting of sufficient amounts of droplets to solid tumors to direct effective mechanical force toward tumor cells remains a major challenge. In this study, we incorporated superparamagnetic iron oxide (SPIO) nanoparticles into acoustic droplets to allow both magnetism-assisted targeting and magnetic resonance (MR)-guided ultrasound-triggered ADV. The multi-functionality of these droplets was further increased by co-encapsulation of the chemotherapeutic drug doxorubicin (DOX) and surface conjugation of anti-vascular endothelial growth factor receptor 2 antibody, to serve as an additional targeting moiety. Maximum loading capacities of 7.69 mg SPIO and 1.53 mg DOX per mL were achieved, and magnetic properties were characterized by determination of magnetic hysteresis curves and transverse relaxation rates. In vitro and in vivo MR imaging demonstrated the feasibility of dual modal imaging of SPIO-embedded droplets. Finally, a vessel-mimicking phantom model with live C6 glioma cells was used to demonstrate a 5.4-fold improvement in targeting efficacy by magnetism-assisted targeting of the SPIO-embedded droplets, and effective disruption of cells by insonation-induced ADV, suggesting the potential of developing this system for future clinical applications.