Innovative melanoma treatment: Acoustic-sensitive foam induces tumor cavitation via the nibbling effect

Melanoma, a malignant tumor originating from melanocytes, is characterized by rapid proliferation and high metastatic potential. Addressing the urgent clinical need for effective tumor-suppressive agents to inhibit melanoma progression, this study introduces a novel therapeutic strategy utilizing acoustic-sensitive foam, termed PFH/TA9. This foam integrates perfluorohexane (PFH), an acoustic-sensitive material, with tranexamic acid nonyl ester hydrochloride (TA9), a cationic surfactant. Administered as an aqueous dispersion, PFH/TA9 was injected directly into the tumor site, where it underwent liquid-to-gas phase transition under low-intensity focused ultrasound radiation. This transition generated PFH bubbles, serving as a gas source for foam formation. The intense ultrasonic cavitation effect induced by LIFU supplied the mechanical force necessary for foam generation, while TA9 molecules aligned at the PFH gas-water interface, reducing surface tension and stabilizing the foam. The stabilized foam extensively contacted tumor tissue, initiating a "nibbling effect" that progressively disrupted tumor cells by damaging cell membranes and inducing tissue cavitation. The acoustic-sensitive foam exhibited a TUNEL⁺ cell rate of 20.91 % and tumor cavitation area of 52.78 % in central tumor regions at 24h post-treatment, achieving 89.37 % tumor inhibition by day 16. By leveraging the cavitation and nibbling effects of acoustic-sensitive foam, this innovative therapeutic strategy demonstrated highly efficient containment of melanoma.