US/MR Bimodal Imaging-Guided Bio-Targeting Synergistic Agent for Tumor Therapy

Abstract

Purpose: Breast cancer is detrimental to the health of women due to the difficulty of early diagnosis and unsatisfactory therapeutic efficacy of available breast cancer therapies. High intensity focused ultrasound (HIFU) ablation is a new method for the treatment of breast tumors, but there is a problem of low ablation efficiency. Therefore, the improvement of HIFU efficiency to combat breast cancer is immediately needed. This study aimed to describe a novel anaerobic bacteria-mediated nanoplatform, comprising synergistic HIFU therapy for breast cancer under guidance of ultrasound (US) and magnetic resonance (MR) bimodal imaging.

Methods: The PFH@CL/Fe₃O₄ nanoparticles (NPs) (Perfluorohexane (PFH) and superparamagnetic iron oxides (SPIO, Fe₃O₄) with cationic lipid (CL) NPs) were synthesized using the thin membrane hydration method. The novel nanoplatform Bifidobacterium bifidum-mediated PFH@CL/Fe₃O₄ NPs were constructed by electrostatic adsorption. Thereafter, US and MR bimodal imaging ability of B. bifidum-mediated PFH@CL/Fe₃O₄ NPs was evaluated in vitro and in vivo. Finally, the efficacy of HIFU ablation based on B. bifidum-PFH@CL/Fe₃O₄ NPs was studied.

Results: B. bifidum combined with PFH@CL/Fe₃O₄ NPs by electrostatic adsorption and enhanced the tumor targeting ability of PFH@CL/Fe₃O₄ NPs. US and MR bimodal imaging clearly displayed the distribution of the bio-targeting nanoplatform in vivo. It was conducive for accurate and effective guidance of HIFU synergistic treatment of tumors. Furthermore, PFH@CL/Fe₃O₄ NPs could form microbubbles by acoustic droplet evaporation and promote efficiency of HIFU ablation under guidance of bimodal imaging.

Conclusion: A bio-targeting nanoplatform with high stability and good physicochemical properties was constructed. The HIFU synergistic agent achieved early precision imaging of tumors and promoted therapeutic effect, monitored by US and MR bimodal imaging during the treatment process.

Keywords: Bifidobacterium bifidum; cancer therapy; high-intensity focused ultrasound; imaging guidance; nanoparticles.