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.