Multi-mechanism antitumor/antibacterial effects of Cu-EGCG self-assembling nanocomposite in tumor nanotherapy and drug-resistant bacterial wound infections

谷胱甘肽 化学 活性氧 单线态氧 光热治疗 激进的 羟基自由基 氧化应激 生物膜 过氧化氢 肿瘤微环境 癌症研究 抗菌活性 组合化学 药理学 生物化学 细菌 氧气 纳米技术 有机化学 材料科学 医学 生物 肿瘤细胞 遗传学
作者
Yinyin Chen,Haoran Li,Nana Liu,Dongju Feng,Wei Wu,Ke Gu,Aimin Wu,Chunxia Li,Xianxiang Wang
出处
期刊:Journal of Colloid and Interface Science [Elsevier]
卷期号:671: 751-769 被引量:5
标识
DOI:10.1016/j.jcis.2024.05.080
摘要

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 (H2O2) and converting to Cu2+. This Cu2+ 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 (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.
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