College of Biomedical Engineering, Sichuan University, Chengdu 610065, China.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China.
J Mater Chem B. 2024 Oct 2;12(38):9686-9694. doi: 10.1039/d4tb00910j.
The hypoxic microenvironment of solid tumors can lead to reduced therapeutic DNA damage to the tumor cells, thus diminishing tumor sensitivity to radiotherapy. Although hypoxic radiosensitizers can improve radiotherapy efficacy by enhancing the role of oxygen, their effects are limited by the uneven distribution of oxygen within solid tumor tissues. In this study, a novel radiosensitizer leveraging gold complexes and metronidazole (MN) was synthesized to improve radiotherapeutic efficacy. The gold atoms incorporated in the radiosensitizer enabled efficient deposition of high-energy radiation; the hydrophobic metronidazole was reduced to hydrophilic aminoimidazole under hypoxia conditions and further promoted radiotherapy sensitization. The results of CCK-8 assays, Live/Dead assays, γ-HAX immunofluorescence indicated that metronidazole-modified Au@BSA nanocomposites (NCs) exhibited excellent antitumor effects. The antitumor tests further showed an inhibition rate of 100%. These results demonstrated that the NCs successfully enhanced radiotherapy efficacy by the dual sensitization strategy. Overall, we believe this multimodal radiosensitizing nanocomplex can significantly inhibit tumor growth and metastasis, with their hypoxia-oriented characteristics ensuring a higher efficacy and safety.
肿瘤的缺氧微环境会导致肿瘤细胞内的治疗性 DNA 损伤减少，从而降低肿瘤对放疗的敏感性。虽然缺氧增敏剂可以通过增强氧气的作用来提高放疗效果，但它们的效果受到实体瘤组织内氧气分布不均的限制。在这项研究中，我们合成了一种利用金配合物和甲硝唑（MN）的新型增敏剂，以提高放射治疗效果。增敏剂中掺入的金原子能够有效地沉积高能射线；在缺氧条件下，疏水性甲硝唑被还原为亲水性氨基咪唑，并进一步促进放射治疗增敏。CCK-8 检测、Live/Dead 检测、γ-HAX 免疫荧光的结果表明，甲硝唑修饰的 Au@BSA 纳米复合物（NCs）具有优异的抗肿瘤效果。抗肿瘤试验进一步显示抑制率达到 100%。这些结果表明，NCs 成功地通过双重增敏策略增强了放疗效果。总的来说，我们相信这种多模式放射增敏纳米复合物可以显著抑制肿瘤生长和转移，其缺氧靶向特性确保了更高的疗效和安全性。
