Comparative analysis of ALA mediated sonodynamic therapy considering tumor size, light combination and ultrasound delivery in murine cutaneous melanoma

Sonodynamic therapy (SDT) is a non-invasive alternative treatment for cancer. However, its effects on early-stage and intradermally implanted melanoma remain underexplored. Here, we investigated the in vivo effects of 5-aminolevulinic acid (ALA)-mediated SDT on early-stage murine cutaneous melanoma. Three comparative analyses were conducted to evaluate: (1) the efficacy of SDT on tumors at two distinct stages–Stage 1 and Stage 2–defined in this study based on Breslow depth: 1–1.5 mm for Stage 1 and 2.5–3 mm for Stage 2; (2) the therapeutic potential of combining SDT with photodynamic therapy (PDT) in Stage 1 tumors; and (3) the effectiveness of two ultrasound delivery approaches–via waveguide and direct contact. SDT induced significant tumor growth inhibition in Stage 1 (86.5%) and Stage 2 (72.5%) tumors compared to controls. The combination of SDT and PDT did not result in significantly greater tumor growth inhibition compared to SDT or PDT alone in Stage 1 tumors. ALA-mediated SDT thus demonstrates potential as a therapeutic strategy for early-stage cutaneous melanoma. However, under the conditions employed, combining SDT with PDT did not enhance therapeutic efficacy. Both waveguide-mediated and direct-contact ultrasound delivery proved effective for treating Stage 2 tumors, with waveguides offering advantages in anatomically challenging regions.