Combination of Proton Therapy and Photodynamic Therapy in Cancer Therapy and Diagnosis

Cancer therapy continues to evolve, with significant advances in precision techniques such as surgery, chemotherapy, immunotherapy, radiotherapy, and photodynamic therapy (PDT). Proton therapy, leveraging the physical properties of the Bragg peak, has revolutionized targeted dose delivery to tumors while minimizing damage to healthy tissue. PDT, which relies on light-activated photosensitizers to generate cytotoxic reactive oxygen species (ROS), introduces molecular specificity but suffers from limitations such as poor light penetration and oxygen dependence. Concurrently, real-time fluorescence and molecular imaging have emerged as pivotal technologies for visualizing tumor margins, optimizing treatment delivery, and assessing response, thereby enhancing the precision of modern oncology. Despite this progress, the seamless integration of these modalities for synergistic, image-guided, highly targeted cancer therapy remains largely untapped.Recent experimental investigations suggest a novel intersection between proton irradiation and PDT. Proton beams may interact with certain photosensitizers to induce secondary electron production, leading to enhanced ROS generation and even photosensitizer excitation independent of external light, a process that also produces measurable fluorescence. This emerging concept of “proton-dynamic” therapy has the potential to address the limitations of each modality alone, offer real-time imaging capabilities, and deliver superior tumor control, while sparing normal tissue and modulating immune responses via molecular pathways such as NRF2 signaling. However, the underlying mechanisms, optimal agents, impact on imaging, translation to preclinical models, and clinical feasibility still demand rigorous investigation.This Research Topic aims to gather pioneering studies that define and expand the scientific, translational, and clinical landscape of integrating proton therapy with photodynamic therapy and fluorescence-based imaging. Key objectives include elucidating the mechanistic interactions between protons and photosensitizers, determining how proton-driven processes can heighten ROS production and imaging contrast, optimizing the choice and delivery of photosensitizers for charged particle activation, and advancing the clinical pipeline from preclinical models to early-phase patient trials. The research will also address questions about immune modulation and normal tissue protection inherent in combined approaches, setting the stage for next-generation theranostic oncology frameworks.To gather further insights in the integration of proton therapy with photochemical and optical imaging modalities, we welcome articles addressing, but not limited to, the following themes:- Mechanistic studies of proton-induced photosensitizer excitation, ROS dynamics, and related microphysics.- Comparative studies in preclinical models across mono and combined proton-PDT approaches.- Development and integration of real-time fluorescence and molecular imaging with proton therapy.- Innovations in dual-function agents, nanomaterials, and theranostic platformsInvestigations of NRF2 signaling, immune modulation, and normal tissue response in proton-dynamic therapy.- Translational and clinical studies, including early feasibility, safety, and patient outcomes.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases that are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this Research Topic. Topic editors: Kave Moloudi, Siamak Haghdoost, Mojtaba Hoseini-Ghahfarokhi, Kolawole A. Olofinsan Source: https://www.frontiersin.org/research-topics/79383/combination-of-proton-therapy-and-photodynamic-therapy-in-cancer-therapy-and-diagnosis