中国科学院大学田志远团队报道了分子光开关解锁葡萄糖氧化酶协同增强芬顿反应，用于抗肿瘤化学动力学治疗。相关研究成果于2024年8月23日发表在国际顶尖学术期刊《德国应用化学》。

研究人员开发了一种新型的纳米粒子，具有强大的抗肿瘤活性，可以通过螺吡喃（SP）的分子光开关和葡萄糖氧化酶（GOx）的酶反应相结合进行光活化。作为其中涉及的两个关键过程，在Fe（III）金属有机框架（MOFs）中，Fe（Ⅲ）-到Fe（Ⅱ）的光还原导致游离Fe²⁺/Fe³⁺的释放，而SP到花青（MC）的光开关释放了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）进一步强化了这一点。基于Fe²⁺和酸性环境的产生以及氧化反应的另一种产物过氧化氢（H₂O₂），这两个过程共同呈现了三重使能因子，通过芬顿反应产生致命的羟基自由基（OH）物种，从而产生能够抑制肿瘤的氧化应激。

这种纳米粒子的抗肿瘤效力在体内荷瘤模型小鼠中得到了验证，基于光学操纵酶活性的独特机制，宣布其作为一种有效和安全的药物的潜力，用于具有高空间精度、增强疗效和最小化副作用的协同抗肿瘤治疗。

附：英文原文

Title: Molecular Photoswitching Unlocks Glucose Oxidase for Synergistically Reinforcing Fenton Reactions for Antitumor Chemodynamic Therapy

Author: Zhiyuan Tian, Zicheng Wang, Weier Bao, Baerlike Wujieti, Ming Liu, Xiaojuan Li, Zhecheng Ma, Wei Cui

Issue&Volume: 2024-08-23

Abstract: 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.

DOI: 10.1002/anie.202413633

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202413633