Terapia sonodinâmica aplicada ao melanoma cutâneo: um estudo pré-clínico em modelo animal

Abstract

Cutaneous melanoma is one of the most aggressive and deadly forms of skin cancer. Sonodynamic therapy (SDT) is a non-invasive alternative anticancer technique based on the interaction between low-intensity ultrasound and a sonoactive molecule, known as a sonosensitizer (SS), in an oxygenated environment. However, the potential of SDT for the treatment of cutaneous melanoma has not yet been widely explored. This study aimed to evaluate the in vivo effects of 5-aminolevulinic acid (ALA)-mediated SDT on early-stage intradermal pigmented melanoma in mice. To establish the tumor model, B16-F10 melanoma cells (10⁶ cells per animal) were intradermally implanted into the right flank of Nu/J athymic mice. Tumors were categorized into two stages based on thickness: stage 1 (1–1.5 mm) and stage 2 (2.5–3 mm). Both groups were treated using a SDT protocol consisting of low-intensity ultrasound (2 W/cm², 100 Hz, 50% duty cycle, 30 minutes) delivered through a conical aluminum waveguide. Tumor thickness and volume were measured daily using high-resolution ultrasound imaging (Vevo 3100 System). Three days after treatment, the animals were euthanized, and the tumors were excised and processed for histological analysis. A significant reduction in tumor volume was observed in both stage 1 and stage 2 groups treated with ALA-mediated SDT, compared to the untreated control group. These findings demonstrate the therapeutic potential of SDT for early-stage cutaneous melanoma. Additionally, the use of a conical waveguide proved beneficial by focusing the ultrasound energy on localized tumor areas, effectively limiting damage to surrounding healthy tissues.