Fan Yue, Yu Shulin, Yang Zhaoshuo, Cai Dingfang
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai, China.
Nanoscale. 2025 Mar 13;17(11):6646-6659. doi: 10.1039/d4nr02406k.
Chemodynamic therapy (CDT) is a therapeutic method that uses a Fenton/Fenton-like reaction to convert intracellular HO into highly cytotoxic ˙OH to effectively kill cancer cells. This method is adapted to the specific characteristics of the tumor microenvironment, boasting high selectivity and strong specificity among other advantages. However, CDT still faces challenges. Glutathione (GSH), which is present in high levels in the tumor microenvironment, can consume a large amount of ˙OH, significantly limiting the effectiveness of CDT. In this study, we synthesized a core-shell nanozyme (mSiO@MnO) with a composite structure comprising a mesoporous silica core and a manganese dioxide (MnO) shell. The mesoporous structure was loaded with the chemotherapeutic drug genistein (Gen) and surface-modified with polyethylene glycol (PEG) to enhance its effectiveness in treating pancreatic cancer. This formulation, denoted as the Gen@mSiO@MnO-PEG nanocomplex enzyme, exhibits a dual action mechanism. Firstly, upon reaching tumor cells, it releases genistein for kinetic therapy and degrades the MnO shell. Secondly, GSH consumption triggers Fenton-like reactions to generate ˙OH, thereby enhancing CDT. At the cellular level, the Gen@mSiO@MnO-PEG nanocomplex enzyme demonstrates excellent biocompatibility. It induces the production of reactive oxygen species in the pancreatic cancer cell line PANC-1, disrupting the redox balance within tumor cells, and ultimately killing them. , the Gen@mSiO@MnO-PEG nanocomplex enzyme selectively accumulates at the tumor sites in PANC-1 tumor-bearing mice, resulting in the inhibition of tumor growth and metastasis. This study demonstrates that core-shell nanozymes serve as an effective platform for cancer therapy, enhancing the efficacy of combined chemotherapy and CDT for pancreatic cancer.
化学动力疗法（CDT）是一种利用芬顿/类芬顿反应将细胞内的H₂O₂转化为具有高细胞毒性的·OH以有效杀死癌细胞的治疗方法。该方法适应肿瘤微环境的特定特征，具有高选择性和强特异性等优点。然而，CDT仍面临挑战。肿瘤微环境中高水平存在的谷胱甘肽（GSH）会消耗大量的·OH，显著限制了CDT的有效性。在本研究中，我们合成了一种具有核壳结构的纳米酶（mSiO₂@MnO₂），其复合结构包括介孔二氧化硅核和二氧化锰（MnO₂）壳。介孔结构负载了化疗药物染料木黄酮（Gen），并通过聚乙二醇（PEG）进行表面修饰，以提高其治疗胰腺癌的效果。这种制剂，称为Gen@mSiO₂@MnO₂-PEG纳米复合酶，具有双重作用机制。首先，到达肿瘤细胞后，它释放染料木黄酮进行动力学治疗并降解MnO₂壳。其次，GSH的消耗触发类芬顿反应生成·OH，从而增强CDT。在细胞水平上，Gen@mSiO₂@MnO₂-PEG纳米复合酶表现出优异的生物相容性。它在胰腺癌细胞系PANC-1中诱导活性氧的产生，破坏肿瘤细胞内的氧化还原平衡，并最终杀死它们。此外，Gen@mSiO₂@MnO₂-PEG纳米复合酶在荷PANC-1肿瘤的小鼠体内肿瘤部位选择性积累，导致肿瘤生长和转移受到抑制。本研究表明，核壳纳米酶作为癌症治疗的有效平台，增强了联合化疗和CDT对胰腺癌的疗效。
