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

Abstract

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.

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

“…Actually, a solution could be to enhance the acoustic power or the exposition time, however it would increase the risk of side effects, as skin burns and nerve injury [47,48]. Thus, various types of micro and nano-bubbles [49], as well as other particles [50], were proposed in combination with HIFU for therapy and diagnostic imaging. These structures are indeed able to enhance HIFU-associated mechanical effects, providing cavitation nuclei [48].…”

<div>Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging</div>

“…The mean particle size and zeta potential were determined by dynamic light scattering (Malvern Instruments, Malvern, UK). PFP nanoemulsions were stored at 4°C, and the mean particle size was measured at different time points after preparation (6,12,18,24,30,36,42,48,54,60,66, and 72 h).…”

“…13 To solve the conflict between US imaging and particle penetration, phase-transition technology was introduced by developing nanoscaled MB precursors that effectively accumulate in tumor tissue by passive or active targeting and then convert into MBs in situ under tumordirected US. 14,15 Notably, our groups recently fabricated PFC nanosystems capable of phase transition that successfully delivered to release drugs and affect gene expression, 16 facilitate multimodal imaging, 17,18 and increase the therapeutic efficiencies of high-intensity focused US (HIFU) and chemoembolization. 19 The liquid-gas phase transition of perfluorohexane (PFH, boiling point [BP] 58°C-60°C) can be triggered by hyperthermia under HIFU; however, this operation is risky and invasive and does not allow intraoperative imaging.…”

A Laser-Activated Biocompatible Theranostic Nanoagent for Targeted Multimodal Imaging and Photothermal Therapy

“…The shell surface was modified with polyethylene glycol (PEG) to prolong blood circulation time and HER2 targeting ligands for targeting HER2 expressing cancer cells. Superparamagnetic iron oxide (SPIO) nanoparticles [32] within the shell enable MR [33][34][35] and PA [36] imaging. Also contained in the shell is 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyan ine iodide (DIR), commonly used as a NIRF contrast agent [37].…”