In Vivo Targeted, Responsive, and Synergistic Cancer Nanotheranostics by Magnetic Resonance Imaging-Guided Synergistic High-Intensity Focused Ultrasound Ablation and Chemotherapy

As one of the most representative noninvasive therapeutic modalities, high-intensity focused ultrasound (HIFU) has shown great promise for cancer therapy, but its low therapeutic efficacy and biosafety significantly hinder further extensive clinical translation and application. In this work, we report on the construction of a multifunctional theranostic nanoplatform to synergistically enhance the HIFU-therapeutic efficacy based on nanomedicine. A targeted and temperature-responsive theranostic nanoplatform (PFH/DOX@PLGA/Fe3O4-FA) has been designed and fabricated for efficient ultrasound/magnetic resonance dual-modality imaging-guided HIFU/chemo synergistic therapy. Especially, the folate was conjugated onto the surface of the nanoplatform for achieving active targeting to hepatoma cells by receptor-ligand interaction, which facilitates accumulation of the nanoplatforms into the tumor site. The integrated superparamagnetic iron oxide nanoparticles could generate the contrast enhancement in T2-weighted magnetic resonance imaging. By virtue of the thermal effect as generated by HIFU, liquid-gas phase transition of perfluorohexane (PFH) in nanocomposites was induced to generate PFH microbubbles, which achieved the contrast-enhanced ultrasound imaging and significantly improved the HIFU ablation efficacy. The loaded anticancer drugs could be released from the nanocomposites in a controllable manner (both pH and HIFU responsiveness). These multifunctional nanocomposites have been demonstrated to efficiently suppress the tumor growth based on the enhanced and synergistic chemotherapy and HIFU ablation, providing an efficient theranostic nanoplatform for cancer treatment.