Non-thermal acoustic treatment as a safe alternative to thermosensitive liposome-involved hyperthermia for cancer therapy

Abstract

A heat-triggered drug release strategy based on ultrasound-assisted mild hyperthermia and thermosensitive liposomes has emerged as a promising option to enable spatiotemporally controlled, efficient drug delivery for cancer treatment. However, consequential thermal vascular damage may decrease drug extravasation into tumor tissue and affect the therapeutic efficacy of follow-up treatments. To overcome this limitation, we explored a non-thermal acoustic treatment. Doxorubicin (DOX), an anticancer drug, was encapsulated in fatty acid-conjugated, elastin-like peptide (FELP)-bearing thermosensitive liposomes (FTSLs) for comparison of two treatments and their therapeutic implications. DOX-FTSLs had an average hydrodynamic size of 134.9 nm with a unimodal distribution. Their thermosensitivity allowed the triggering of rapid DOX release at 42 °C, a mild-hyperthermia relevant temperature, with sustained DOX release at 37 °C. Interestingly, non-thermal acoustic treatment right after systemic administration of DOX-FTSLs into tumor-bearing mice led to higher tissue penetration without permanent vascular damage, greater intratumoral DOX accumulation, and similar therapeutic efficacy to thermal treatment. Overall, non-thermal acoustic treatment may be a safe alternative to thermosensitive liposome-involved hyperthermia for liposomal chemotherapy.