College of Agronomy, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China.
J Colloid Interface Sci. 2024 Oct;671:751-769. doi: 10.1016/j.jcis.2024.05.080. Epub 2024 May 19.
Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor's adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (HO) and converting to Cu. This Cu interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG's efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (O) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.
化疗和手术是癌症的主要治疗方法，但肿瘤微环境的独特特征阻碍了它们的疗效。天然化合物表没食子儿茶素没食子酸酯（EGCG）具有很强的抗肿瘤和抗菌特性。然而，由于肿瘤的酸性 pH 值和升高的谷胱甘肽（GSH）水平，肿瘤对化疗的适应性，加上手术后耐药细菌感染的挑战，阻碍了治疗效果。为了解决这些挑战，研究人员努力探索创新的治疗策略，如多模式联合治疗。本研究成功合成了 Cu-EGCG，一种金属多酚网络，并通过同步辐射和高分辨率质谱（HRMS）详细表征了它。通过化学动力学治疗（CDT）、光热治疗（PTT）和光动力治疗（PDT），Cu-EGCG 表现出强大的抗肿瘤和抗菌作用。Cu-EGCG 中的 Cu 积极参与芬顿样反应，在暴露于过氧化氢（HO）时生成羟基自由基（·OH），并转化为 Cu。这种 Cu 与 GSH 相互作用，削弱了细菌和肿瘤细胞的氧化应激反应。密度泛函理论（DFT）计算验证了 Cu-EGCG 在与 GSH 反应时有效消耗 GSH。此外，Cu-EGCG 在暴露于 808nm 近红外（NIR）辐射时表现出出色的光热转换，并在激光照射下产生单线态氧（O）。在小鼠肿瘤和伤口模型中，Cu-EGCG 表现出显著的抗肿瘤和抗菌特性。
