Department of Radiology, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, P. R. China.
Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, P. R. China.
Adv Sci (Weinh). 2023 Oct;10(30):e2302141. doi: 10.1002/advs.202302141. Epub 2023 Sep 8.
Radiotherapy (RT), a widely used clinical treatment modality for cancer, uses high-energy irradiation for reactive oxygen species (ROS) production and DNA damage. However, its therapeutic effect is primarily limited owing to insufficient DNA damage to tumors and harmful effects on normal tissues. Herein, a core-shell structure of metal-semiconductors (Au@AgBiS nanoparticles) that can function as pyroptosis inducers to both kill cancer cells directly and trigger a robust anti-tumor immune against 4T1 triple-negative murine breast cancer and metastasis is rationally designed. Metal-semiconductor composites can enhance the generation of considerable ROS and simultaneously DNA damage for RT sensitization. Moreover, Au@AgBiS , a pyroptosis inducer, induces caspase-3 protein activation, gasdermin E cleavage, and the release of damage-associated molecular patterns. In vivo studies in BALB/c mice reveal that Au@AgBiS nanoparticles combined with RT exhibit remarkable antitumor immune activity, preventing tumor growth, and lung metastasis. Therefore, this core-shell structure is an alternative for designing highly effective radiosensitizers for radioimmunotherapy.
放疗（RT）是一种广泛应用于癌症的临床治疗方法，利用高能射线产生活性氧（ROS）和 DNA 损伤。然而，由于肿瘤内 DNA 损伤不足以及对正常组织的有害影响，其治疗效果主要受到限制。在此，合理设计了一种金属-半导体（Au@AgBiS 纳米粒子）的核壳结构，可作为细胞焦亡诱导剂，直接杀死癌细胞，并引发针对 4T1 三阴性乳腺癌和转移的强烈抗肿瘤免疫。金属-半导体复合材料可以增强大量 ROS 的产生，并同时对 DNA 损伤进行 RT 增敏。此外，细胞焦亡诱导剂 Au@AgBiS 诱导 caspase-3 蛋白激活、gasdermin E 切割以及损伤相关分子模式的释放。在 BALB/c 小鼠体内研究中，Au@AgBiS 纳米粒子与 RT 联合使用表现出显著的抗肿瘤免疫活性，可防止肿瘤生长和肺转移。因此，这种核壳结构为设计高效的放免联合治疗用放射增敏剂提供了一种替代方案。
