We have developed a new type of nanoparticles with potent antitumor activity photoactivatable via the combination of molecular photoswitching of spiropyran (SP) and enzymatic reaction of glucose oxidase (GOx). As two key processes involved therein, Fe(III)‐to‐Fe(II) photoreduction in Fe(III) metal‐organic frameworks (MOFs) brings about the release of free Fe2+/Fe3+ while the photoswitching of SP to merocyanine (MC) unlocks the enzymatic activity of GOx that was pre‐passivated by SP. The release of free Fe3+ boosts its hydrolysis and therefore enables the acidification of microenvironment, which is further reinforced by one of the products of the GOx‐mediated glucose oxidation reaction, gluconic acid (GlcA). Based on the generation of Fe2+ and acidic milieu together with another product of the oxidation reaction, hydrogen peroxide (H2O2), these two processes jointly present triple enabling factors for generating lethal hydroxyl radicals (•OH) species via Fenton reactions and therefore oxidative stress capable of inhibiting tumor. The antitumor potency of such nanoparticle is verified in tumor‐bearing model mice in vivo, proclaiming its potential as a potent and safe agent based on the unique mechanism of optically manipulating enzyme activity for synergistic antitumor therapeutics with high spatial precision, enhanced efficacy and minimized side effects.

中文翻译：

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分子光开关解锁葡萄糖氧化酶，协同增强抗肿瘤化学动力学治疗的芬顿反应


我们通过螺吡喃（SP）的分子光开关和葡萄糖氧化酶（GOx）的酶促反应的结合，开发了一种具有强效抗肿瘤活性的新型纳米颗粒，可光激活。作为其中涉及的两个关键过程，Fe(III)金属有机框架(MOF)中的Fe(III)-to-Fe(II)光还原导致游离Fe2+/Fe3+的释放，同时SP光转换为部花青(MC)解锁由 SP 预钝化的 GOx 的酶活性。游离 Fe3+ 的释放促进了其水解，从而使微环境酸化，而 GOx 介导的葡萄糖氧化反应的产物之一葡萄糖酸 (GlcA) 进一步增强了微环境的酸化。基于 Fe2+ 和酸性环境以及氧化反应的另一种产物过氧化氢 (H2O2) 的生成，这两个过程共同呈现出通过芬顿反应生成致命羟基自由基 (·OH) 物种的三重促成因素，因此能够产生氧化应激具有抑制肿瘤的作用。这种纳米粒子的抗肿瘤效力在荷瘤模型小鼠体内得到验证，基于光学操纵酶活性的独特机制，可实现协同抗肿瘤治疗，具有高空间精度、增强功效和最小化副作用，证明其作为有效且安全的药物的潜力影响。