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

Abstract 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...

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Main Authors: Erika Toneth Ponce Ayala, Iago Silva e Carvalho, Camila Aparecida Antunes, Aisha Mahmood, Michelle Barreto Requena, Fernanda Alves, Layla Pires, Vladislav Yakovlev, Vanderlei Salvador Bagnato, Sebastião Pratavieira
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Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-16366-x
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author Erika Toneth Ponce Ayala
Iago Silva e Carvalho
Camila Aparecida Antunes
Aisha Mahmood
Michelle Barreto Requena
Fernanda Alves
Layla Pires
Vladislav Yakovlev
Vanderlei Salvador Bagnato
Sebastião Pratavieira
author_facet Erika Toneth Ponce Ayala
Iago Silva e Carvalho
Camila Aparecida Antunes
Aisha Mahmood
Michelle Barreto Requena
Fernanda Alves
Layla Pires
Vladislav Yakovlev
Vanderlei Salvador Bagnato
Sebastião Pratavieira
author_sort Erika Toneth Ponce Ayala
collection DOAJ
description Abstract 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.
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spelling doaj-art-60d63db695d240cda2f24c3fa4e542852025-08-24T11:17:04ZengNature PortfolioScientific Reports2045-23222025-08-0115111910.1038/s41598-025-16366-xComparative analysis of ALA mediated sonodynamic therapy considering tumor size, light combination and ultrasound delivery in murine cutaneous melanomaErika Toneth Ponce Ayala0Iago Silva e Carvalho1Camila Aparecida Antunes2Aisha Mahmood3Michelle Barreto Requena4Fernanda Alves5Layla Pires6Vladislav Yakovlev7Vanderlei Salvador Bagnato8Sebastião Pratavieira9São Carlos Institute of Physics, University of São PauloSão Carlos Institute of Physics, University of São PauloSão Carlos Institute of Physics, University of São PauloDepartment of Biomedical Engineering, Texas A&M UniversitySão Carlos Institute of Physics, University of São PauloSão Carlos Institute of Physics, University of São PauloDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversitySão Carlos Institute of Physics, University of São PauloSão Carlos Institute of Physics, University of São PauloAbstract 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.https://doi.org/10.1038/s41598-025-16366-xSonodynamicPhotodynamic5-aminolevulinic acidProtoporphyrin IXMelanoma
spellingShingle Erika Toneth Ponce Ayala
Iago Silva e Carvalho
Camila Aparecida Antunes
Aisha Mahmood
Michelle Barreto Requena
Fernanda Alves
Layla Pires
Vladislav Yakovlev
Vanderlei Salvador Bagnato
Sebastião Pratavieira
Comparative analysis of ALA mediated sonodynamic therapy considering tumor size, light combination and ultrasound delivery in murine cutaneous melanoma
Scientific Reports
Sonodynamic
Photodynamic
5-aminolevulinic acid
Protoporphyrin IX
Melanoma
title Comparative analysis of ALA mediated sonodynamic therapy considering tumor size, light combination and ultrasound delivery in murine cutaneous melanoma
title_full Comparative analysis of ALA mediated sonodynamic therapy considering tumor size, light combination and ultrasound delivery in murine cutaneous melanoma
title_fullStr Comparative analysis of ALA mediated sonodynamic therapy considering tumor size, light combination and ultrasound delivery in murine cutaneous melanoma
title_full_unstemmed Comparative analysis of ALA mediated sonodynamic therapy considering tumor size, light combination and ultrasound delivery in murine cutaneous melanoma
title_short Comparative analysis of ALA mediated sonodynamic therapy considering tumor size, light combination and ultrasound delivery in murine cutaneous melanoma
title_sort comparative analysis of ala mediated sonodynamic therapy considering tumor size light combination and ultrasound delivery in murine cutaneous melanoma
topic Sonodynamic
Photodynamic
5-aminolevulinic acid
Protoporphyrin IX
Melanoma
url https://doi.org/10.1038/s41598-025-16366-x
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