A continuous tri-phase transition effect for HIFU-mediated intravenous drug delivery

Aiming at substantially enhanced efficacy and biosafety of clinical HIFU therapy, a natural solid medium, L-menthol (LM), characteristic of mild and controllable “solid-liquid-gas” (SLG) tri-phase transition, was adopted, instead of those conventional explosive liquid-gas (LG) bi-phase transitional media, in constructing a multifunctional theranostic system. Owing to the continuous and controllable characteristics of SLG tri-phase transition, such a novel tri-phase transition-based theranostic system has been demonstrated of the repeatedly enhanced HIFU efficacy ex vivo and in vivo under once intravenous injection and the significantly improved treatment precision, controllability and biosafety when comparing to the traditional bi-phase transition medium, perfluorohexane (PFH), thus promising great application potential in clinical HIFU treatment. Moreover, this theranostic system has been demonstrated a long blood-circulation lifetime and continuous accumulation in tumor in 24 h, which is very beneficial for the enhanced tumor ablation in vivo along with SLG tri-phase transition. More importantly, after loading multiple model drugs and real drug, such a theranostic system presents a HIFU-mediated temperature-responsive drug release property, and depending on the versatile miscibility of LM, co-loadings with hydrophobic and hydrophilic drugs are also achieved, which provides the possibility of synergistic treatment combining HIFU therapy and chemotherapy.