Induction of an anti-tumor immune response by sonodynamic therapy, combining 5-aminolevulinic acid and high-intensity focused ultrasound using the trigger pulse sonication

Ultrasound-based cancer therapies offer non-invasive treatment options for deep-seated tumors, yet their clinical application is often limited by safety concerns. High-intensity focused ultrasound (HIFU) has demonstrated therapeutic potential, but its high-power requirements can damage surrounding h...

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Main Authors: Tohru Satoh, Rui Tada, Taiki Yamaguchi, Yoko Endo-Takahashi, Takashi Kanno, Mai Hayakawa, Yoshiyuki Adachi, Yoichi Negishi, Jun Okamoto, Shin Yoshizawa, Ken Masamune
Format: Article
Language:English
Published: Elsevier 2025-12-01
Series:WFUMB Ultrasound Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S2949668325000102
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author Tohru Satoh
Rui Tada
Taiki Yamaguchi
Yoko Endo-Takahashi
Takashi Kanno
Mai Hayakawa
Yoshiyuki Adachi
Yoichi Negishi
Jun Okamoto
Shin Yoshizawa
Ken Masamune
author_facet Tohru Satoh
Rui Tada
Taiki Yamaguchi
Yoko Endo-Takahashi
Takashi Kanno
Mai Hayakawa
Yoshiyuki Adachi
Yoichi Negishi
Jun Okamoto
Shin Yoshizawa
Ken Masamune
author_sort Tohru Satoh
collection DOAJ
description Ultrasound-based cancer therapies offer non-invasive treatment options for deep-seated tumors, yet their clinical application is often limited by safety concerns. High-intensity focused ultrasound (HIFU) has demonstrated therapeutic potential, but its high-power requirements can damage surrounding healthy tissues, particularly near sensitive structures such as the gastrointestinal tract. The optimal balance between therapeutic efficacy and safety remains a significant challenge in ultrasound-based cancer treatment. Here we show that combining 5-aminolevulinic acid (5-ALA)-mediated sonodynamic therapy (SDT) with a novel HIFU system achieves effective tumor suppression at reduced acoustic intensities while enhancing anti-tumor immune responses. This novel system features the use of a trigger HIFU sequence that enables precise control over cavitation bubbles within the target tissue. In a murine colon carcinoma model, this approach demonstrated significant tumor growth inhibition with single-session treatment comparable to multiple HIFU sessions, while increasing tumor infiltration by activated CD8+ T cells and antigen-presenting dendritic cells. These findings extend beyond previous studies by revealing that SDT not only enables effective tumor treatment at lower, safer acoustic intensities but also promotes beneficial immune responses that could enhance therapeutic outcomes. This combination of reduced treatment intensity, shortened duration, and immune system activation suggests potential applications for treating tumors in anatomically sensitive locations. The demonstrated immunological effects also indicate possible synergies with existing cancer immunotherapies, potentially expanding treatment options for patients with deep-seated solid tumors.
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spelling doaj-art-c4174d8a792447f5b36c3e9cd25c37ac2025-08-20T02:01:58ZengElsevierWFUMB Ultrasound Open2949-66832025-12-013210008810.1016/j.wfumbo.2025.100088Induction of an anti-tumor immune response by sonodynamic therapy, combining 5-aminolevulinic acid and high-intensity focused ultrasound using the trigger pulse sonicationTohru Satoh0Rui Tada1Taiki Yamaguchi2Yoko Endo-Takahashi3Takashi Kanno4Mai Hayakawa5Yoshiyuki Adachi6Yoichi Negishi7Jun Okamoto8Shin Yoshizawa9Ken Masamune10Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, Japan; Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; SONIRE Therapeutics Inc., Tokyo, Japan; Corresponding author. Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, 8-1 Kawada-Cho, Shinjuku-ku, Tokyo 162-8666, Japan.Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, JapanDepartment of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, JapanDepartment of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, JapanLaboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, JapanLaboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, JapanLaboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, JapanDepartment of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, JapanSONIRE Therapeutics Inc., Tokyo, JapanCommunications Engineering, Tohoku University Graduate School of Engineering, Sendai, Japan; SONIRE Therapeutics Inc., Tokyo, JapanAdvanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, JapanUltrasound-based cancer therapies offer non-invasive treatment options for deep-seated tumors, yet their clinical application is often limited by safety concerns. High-intensity focused ultrasound (HIFU) has demonstrated therapeutic potential, but its high-power requirements can damage surrounding healthy tissues, particularly near sensitive structures such as the gastrointestinal tract. The optimal balance between therapeutic efficacy and safety remains a significant challenge in ultrasound-based cancer treatment. Here we show that combining 5-aminolevulinic acid (5-ALA)-mediated sonodynamic therapy (SDT) with a novel HIFU system achieves effective tumor suppression at reduced acoustic intensities while enhancing anti-tumor immune responses. This novel system features the use of a trigger HIFU sequence that enables precise control over cavitation bubbles within the target tissue. In a murine colon carcinoma model, this approach demonstrated significant tumor growth inhibition with single-session treatment comparable to multiple HIFU sessions, while increasing tumor infiltration by activated CD8+ T cells and antigen-presenting dendritic cells. These findings extend beyond previous studies by revealing that SDT not only enables effective tumor treatment at lower, safer acoustic intensities but also promotes beneficial immune responses that could enhance therapeutic outcomes. This combination of reduced treatment intensity, shortened duration, and immune system activation suggests potential applications for treating tumors in anatomically sensitive locations. The demonstrated immunological effects also indicate possible synergies with existing cancer immunotherapies, potentially expanding treatment options for patients with deep-seated solid tumors.http://www.sciencedirect.com/science/article/pii/S2949668325000102high-intensity focused ultrasoundsonodynamic therapy5-Aminolevulinic acidprotoporphyrin IXreactive oxygen speciestumor immunity
spellingShingle Tohru Satoh
Rui Tada
Taiki Yamaguchi
Yoko Endo-Takahashi
Takashi Kanno
Mai Hayakawa
Yoshiyuki Adachi
Yoichi Negishi
Jun Okamoto
Shin Yoshizawa
Ken Masamune
Induction of an anti-tumor immune response by sonodynamic therapy, combining 5-aminolevulinic acid and high-intensity focused ultrasound using the trigger pulse sonication
WFUMB Ultrasound Open
high-intensity focused ultrasound
sonodynamic therapy
5-Aminolevulinic acid
protoporphyrin IX
reactive oxygen species
tumor immunity
title Induction of an anti-tumor immune response by sonodynamic therapy, combining 5-aminolevulinic acid and high-intensity focused ultrasound using the trigger pulse sonication
title_full Induction of an anti-tumor immune response by sonodynamic therapy, combining 5-aminolevulinic acid and high-intensity focused ultrasound using the trigger pulse sonication
title_fullStr Induction of an anti-tumor immune response by sonodynamic therapy, combining 5-aminolevulinic acid and high-intensity focused ultrasound using the trigger pulse sonication
title_full_unstemmed Induction of an anti-tumor immune response by sonodynamic therapy, combining 5-aminolevulinic acid and high-intensity focused ultrasound using the trigger pulse sonication
title_short Induction of an anti-tumor immune response by sonodynamic therapy, combining 5-aminolevulinic acid and high-intensity focused ultrasound using the trigger pulse sonication
title_sort induction of an anti tumor immune response by sonodynamic therapy combining 5 aminolevulinic acid and high intensity focused ultrasound using the trigger pulse sonication
topic high-intensity focused ultrasound
sonodynamic therapy
5-Aminolevulinic acid
protoporphyrin IX
reactive oxygen species
tumor immunity
url http://www.sciencedirect.com/science/article/pii/S2949668325000102
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