Revolutionary x-ray-sensitizers could transform cancer treatment with low-dose radiation therapy

Researchers at Xiamen University have made a significant advancement in cancer treatment by developing a novel class of X-ray-sensitizers (XSs) that could revolutionize radiotherapy. Published in Engineering, their groundbreaking study highlights how specific organic pharmaceutical drug intermediates, derived from thioxanthone (TX), can be activated by low-dose X-rays to efficiently generate singlet oxygen for targeted cancer therapy.

Traditional radiotherapy, a cornerstone in cancer treatment, often involves high doses of radiation (typically over 50 Gy), which can lead to severe side effects. To mitigate these risks, clinicians frequently employ fractionated radiation therapy, using smaller doses (< 2 Gy) across multiple sessions. The new research by Hongmin Chen’s team proposes an innovative method to enhance the efficacy of these smaller doses, potentially reducing the risk of adverse effects while maintaining or even improving therapeutic outcomes.

The research focuses on TX-derived organic molecules, which have shown remarkable potential in populating triplet excitons—specifically singlet oxygen—under X-ray irradiation. This process, known as scintillator X-ray-induced photodynamic therapy, utilizes low-dose X-ray irradiation to activate these molecules, leading to the generation of singlet oxygen. Singlet oxygen is a highly reactive species that can selectively target and destroy cancer cells, offering a more precise and less harmful alternative to conventional radiotherapy.

The team systematically screened various pharmaceutical drug intermediates that are derivatives of TX. By modifying alkoxy side chain substitutions at the 2-position of TX, they were able to fine-tune the molecular packing and intermolecular interactions. This meticulous adjustment allowed them to assess the fluorescence and room-temperature phosphorescence (RTP) of these TX derivatives under X-ray irradiation.

Their findings reveal that TX derivatives exhibit superior radioluminescence compared to phenothiazine with similar substitutions. Notably, these TX-derived molecules demonstrated a high efficiency in X-ray-sensitization, generating singlet oxygen in response to low-dose X-ray exposure. This capability is pivotal for effective cancer treatment, as it means that a large number of triplet states can be populated directly under minimal radiation, potentially reducing the overall radiation dose required for treatment.

The researchers conducted extensive evaluations of these molecules’ potential for tumor treatment both in vitro and in vivo. The TX derivatives’ ability to generate singlet oxygen and their effectiveness in targeting tumors underscore a promising new avenue for cancer therapy. This breakthrough could lead to the development of a new class of organic molecules designed specifically for low-dose X-ray radiotherapy, enhancing treatment efficacy while minimizing side effects.

This innovative approach opens up new possibilities for improving cancer treatment protocols. With further research and development, these TX-derived XSs could become a key component in advanced cancer therapies, providing a more effective and patient-friendly alternative to current radiotherapy methods.

The paper “X-Ray-Sensitizers: Organic Pharmaceutical Drug Intermediates Activated Directly by X-Rays to Efficiently Populate Triplet Excitons for Cancer Treatment,” authored by Nuo Lin, Han Xu, Haichao Liu, Xiaoqian Ma, Qunying Shi, Qing Yang, Yating Wen, Huanglei Wei, Ke Hu, Bing Yang, Hongmin Chen. Full text of the open access paper: https://doi.org/10.1016/j.eng.2024.06.010. For more information about the Engineering, follow us on X (https://twitter.com/EngineeringJrnl) & like us on Facebook (https://www.facebook.com/EngineeringJrnl).