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Evolution of Particle Radiotherapy: From Physical to Dual Targeting in Precision Medicine
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    Evolution of Particle Radiotherapy: From Physical to Dual Targeting in Precision Medicine
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    • Heying Yao
      Heying Yao
      Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China
      Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha 410013, PR China
      More by Heying Yao
    • Fan Zheng
      Fan Zheng
      Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China
      Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha 410013, PR China
      More by Fan Zheng
    • Yan Zhong
      Yan Zhong
      Zhejiang Cancer Hospital, The Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China
      More by Yan Zhong
    • Huanfeng Tian
      Huanfeng Tian
      Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China
      Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha 410013, PR China
      More by Huanfeng Tian
    • Zhiyan Li
      Zhiyan Li
      Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China
      Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha 410013, PR China
      More by Zhiyan Li
    • Hua Zhu
      Hua Zhu
      Department of Nuclear Medicine, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, Beijing 100142, China
      More by Hua Zhu
    • Zhi Yang
      Zhi Yang
      Department of Nuclear Medicine, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, Beijing 100142, China
      More by Zhi Yang
      Orcidhttps://orcid.org/0000-0003-2084-5193
    • Hong Zhang
      Hong Zhang
      Zhejiang Cancer Hospital, The Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China
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    • Mei Tian
      Mei Tian
      Huashan Hospital & Human Phenome Institute, Fudan University, 825 Zhangheng Road, Shanghai 201203, China
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    • Wenbin Zeng*
      Wenbin Zeng
      Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China
      Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha 410013, PR China
      *E-mail: [email protected]
      More by Wenbin Zeng
      Orcidhttps://orcid.org/0000-0001-8314-9174
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    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2026, XXXX, XXX, XXX-XXX
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    https://doi.org/10.1021/acs.molpharmaceut.6c00111
    Published March 30, 2026
    © 2026 American Chemical Society
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    Abstract

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    As cancer remains a formidable global health challenge, radiotherapy is evolving toward unprecedented levels of precision. Particle radiotherapy (PRT), utilizing charged particles such as protons and carbon ions, has emerged as a superior alternative to conventional photon-based approaches. While proton therapy (PT) achieves superior physical targeting via the Bragg peak and carbon ion radiotherapy (CIRT) adds biological potency through high linear energy transfer (LET), both modalities are fundamentally constrained by their primary reliance on spatial/macroscopic dose distribution. Against this backdrop, boron neutron capture therapy (BNCT) stands out as an innovative dual-targeting strategy in precision oncology. BNCT combines biochemical selectivity (achieved via tumor-specific boron-10 agents) with cellular-scale physical precision (realized by neutron-irradiation-triggered, locally confined high LET particles). This review delineates the latest progress in particle radiotherapy, specifically highlighting the crucial transition from the established physical targeting of PT and CIRT to the burgeoning dual-targeting innovation of BNCT. We provide an in-depth analysis of mechanistic principles, technological advancements in accelerator-based sources, the pharmacological evolution of boron delivery systems, and the resulting clinical applications. Future directions for the entire particle radiotherapy field center on reducing operational costs, optimizing therapeutic accuracy, conducting robust randomized trials, and exploring synergistic therapies. Critically, BNCT, with its unique dual-targeting mechanism, represents a potentially transformative precision therapy with significant potential for intractable malignancies.

    © 2026 American Chemical Society

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    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2026, XXXX, XXX, XXX-XXX
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.molpharmaceut.6c00111
    Published March 30, 2026
    © 2026 American Chemical Society
    Request reuse permissions

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