Ag nanoparticles, a widely used antimicrobial agent, have been recently found to show unexpected anticancer effects. However, its medical applications in anticancer and antibacterial field are significantly hindered due to the size-dependent bioactivity. Considering the close relationship between tumor incidence and infection, herein, we reported the controlled encapsulation of large-size single Ag nanocube (50 nm) in zeolitic imidazolate frameworks (ZIF), accompanied with embedding of glucose oxidase (GOD). The obtained GOD/Ag@ZIF could act as Ag nano-factory to generate ultrasmall Ag NPs (5 nm) as a response to tumor microenvironment. Specifically, GOD-induced generated H₂O₂ in glycolysis continuously decomposed AgNC into Ag⁺ and ultrasmall Ag NPs, where biocompatible ZIF-8 acted as the porous support for Ag⁺ and Ag NPs formation. Further, the GOD/Ag@ZIF were coated with hyaluronic acid (HA), termed by GOD/Ag@ZIF-HA, to allow the nanocomposites with good biocompatibility and target ability. GOD/Ag@ZIF-HA could completely suppress growth of two model bacteria strains at low concentration (E. coli. for 5 μg/mL, S. aureus for 10 μg/mL). More importantly, the high-performance anticancer activity of GOD/Ag@ZIF-HA and the underlying mechanism was also elaborated based on MCF-7 breast tumor model. We believe this study presents enticing possibilities to break through the size restriction of Ag NPs in biomedicine application.

最近发现，广泛使用的抗菌剂Ag纳米粒子显示出出乎意料的抗癌作用。然而，由于其大小依赖性的生物活性，其在抗癌和抗菌领域的医学应用受到了极大的阻碍。考虑到肿瘤发生率和感染之间的密切关系，在本文中，我们报道了在沸石咪唑酸盐骨架（ZIF）中大型单Ag纳米立方体（50 nm）的受控包封，并嵌入了葡萄糖氧化酶（GOD）。获得的GOD / Ag @ ZIF可以作为Ag纳米工厂，以产生超小的Ag NPs（5 nm）作为对肿瘤微环境的响应。具体而言，在糖酵解中，GOD诱导生成的H ₂ O ₂连续地将AgNC分解为Ag ⁺和超小型Ag NP，其中生物相容性ZIF-8充当Ag ⁺和Ag NP形成的多孔载体。此外，用透明质酸（HA）（称为GOD / Ag @ ZIF-HA）涂覆GOD / Ag @ ZIF，以使纳米复合材料具有良好的生物相容性和靶向能力。GOD / Ag @ ZIF-HA可以完全抑制两种模型细菌菌株在低浓度下的生长（大肠杆菌为5μg/ mL，金黄色葡萄球菌为10μg/ mL）。更重要的是，还基于MCF-7乳腺肿瘤模型详细阐述了GOD / Ag @ ZIF-HA的高性能抗癌活性及其潜在机制。我们相信这项研究提供了诱人的可能性，可以突破生物医学应用中Ag NPs的尺寸限制。