Iodinated Copper–Cysteamine Nanoparticles as Radiosensitizers for Tumor Radiotherapy

<b>Background/Objectives:</b> Radiotherapy is a widely applied first-line clinical treatment modality of cancer. Copper–cysteamine (Cu-Cy) nanoparticles represent a new type of photosensitizer that demonstrates significant anti-tumor potential by X-ray-induced photodynamic therapy. Iodid...

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Main Authors: Miaomiao Zhang, Yu Yang, Ying Xu, Jie Wang, Shihong Li
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/2/149
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Summary:<b>Background/Objectives:</b> Radiotherapy is a widely applied first-line clinical treatment modality of cancer. Copper–cysteamine (Cu-Cy) nanoparticles represent a new type of photosensitizer that demonstrates significant anti-tumor potential by X-ray-induced photodynamic therapy. Iodide is a high-Z element with superior X-ray absorption ability and has the β-decay radiotherapeutic nuclide, <sup>131</sup>I, which emits Cherenkov light. In this study we aimed to investigate the X-ray-induced photodynamic therapy potential of iodinated Cu-Cy (Cu-Cy-I) nanoparticles and also explore the local treatment efficacy of <sup>131</sup>I-labeled Cu-Cy-I ([<sup>131</sup>I]Cu-Cy-I) nanoparticles. <b>Methods</b>: The synthesis of [<sup>131</sup>I]Cu-Cy-I nanoparticles was performed with [<sup>131</sup>I]I<sup>−</sup> anions. The in vitro radiobiological effects on tumor cells incubated with Cu-Cy-I nanoparticles by X-ray irradiation were investigated. The in vivo tumor growth-inhibitory effects of the combination of Cu-Cy-I nanoparticles with X-ray radiotherapy and [<sup>131</sup>I]Cu-Cy-I nanoparticles were evaluated with 4T1 tumor-xenografted mice. <b>Results</b>: The in vitro experiment results indicated that the X-ray irradiation with the presence of Cu-Cy-I nanoparticles produced a higher intracellular reactive oxygen species (ROS) level and more DNA damage of 4T1 cells and showed a stronger tumor cell killing ability compared to X-ray irradiation alone. The in vivo experimental results with 4T1 breast carcinoma-bearing mice showed that the combination of an intratumoral injection of Cu-Cy-I nanoparticles and X-ray radiotherapy enhanced the tumor growth-inhibitory effect and prolonged the mice’s lives. <b>Conclusions</b>: Cu-Cy-I nanoparticles have good potential as new radiosensitizers to enhance the efficacy of external X-ray radiotherapy. However, the efficacy of local treatment with [<sup>131</sup>I]Cu-Cy-I nanoparticles at a low <sup>131</sup>I dose was not verified. The effective synthesis of smaller sizes of nanoparticles is necessary for further investigation of the radiotherapy potential of [<sup>131</sup>I]Cu-Cy-I nanoparticles.
ISSN:1999-4923