Nanoparticle-enhanced synergistic HIFU ablation and transarterial chemoembolization for efficient cancer therapy.

High-intensity focused ultrasound (HIFU) is being generally explored as a non-invasive therapeutic modality to treat solid tumors. However, the clinical use of HIFU for large and deep tumor-ablation applications such as hepatocellular carcinoma (HCC) is currently entangled with long treatment duration and high operating energy. This critical issue can be potentially resolved by the introduction of HIFU synergistic agents (SAs). Traditional SAs such as microbubbles and microparticles face the problem of large size, short cycle time, damage to mononuclear phagocytic system and unsatisfactory targeting efficiency. In this work, we have developed a facile and versatile nanoparticle-based HIFU synergistic cancer surgery enhanced by transarterial chemoembolization for high-efficiency HCC treatment based on elaborately designed Fe3O4-PFH/PLGA nanocapsules. Multifunctional Fe3O4-PFH/PLGA nanocapsules were administrated into tumor tissues via transarterial injection combined with Lipiodol to achieve high tumor accumulation because transarterial chemoembolization by Lipiodol could block the blood vessels. The high synergistic HIFU ablation effect was successfully achieved against HCC tumors based on the phase-transformation performance of the perfluorohexane (PFH) inner core in the composite nanocapsules, as systematically demonstrated in VX2 liver tumor xenograft in rabbits. Multifunctional Fe3O4-PFH/PLGA nanocapsules were also demonstrated as efficient contrast agents for ultrasound, magnetic resonance and photoacoustic tri-modality imagings, potentially applicable for imaging-guided HIFU synergistic surgery. Therefore, the elaborate integration of traditional transarterial chemoembolization with recently developed nanoparticle-enhanced HIFU cancer surgery could efficiently enhance the HCC cancer treatment outcome, initiating a new and efficient therapeutic protocol/modality for clinic cancer treatment.