Adv. Funct. Mater. 2019, 1902127

 

天然葡萄糖氧化酶（GOx）已经成为一种与癌症治疗有关的“明星”酶催化剂，因为它能有效地催化β-D-葡萄糖氧化反应生成葡萄糖酸和H₂O₂ ，这种催化反应不仅可以消耗肿瘤的营养物质葡萄糖，同时生成的过氧化氢还可以进一步用于癌症治疗，如气体疗法，金属离子疗法，化学动力学治疗（CDT）等，导致多模态癌症协同作用治疗。这种多级的肿瘤治疗效果明显优于单独治疗，因此级联反应将成为肿瘤治疗的新趋势。

     近日，深圳大学黄鹏团队在ACS Nano 上发表了掺杂Mn²⁺的可生物降解钙磷盐通过级联反应增强肿瘤治疗，掺杂Mn²⁺ 的GOx通过生物矿化形成球形纳米颗粒（GOx MnCaP NPs），然后加载阿霉素（DOX）构建可生物降解的肿瘤酸性反应纳米级联癌症治疗体系。GOx可消耗葡萄糖用于肿瘤饥饿治疗，产生的过氧化氢可与Mn²⁺发生类芬顿反应，生成剧毒的羟基自由基用于化学动力治疗，葡萄糖酸产生的酸度将反过来加速纳米平台的降解，促进Mn²⁺的生成同时，释放出的Mn²⁺离子可用于MRI监测治疗效果。

 

The natural glucose oxidase (GOx) has become a “star” enzyme catalyst involved in cancer treatment, since it can specially and efficiently catalyze the

oxidization reaction of β-D-glucose to generate gluconic acid and H2O2.4 Not only can this catalytic reaction starve the tumors by the consumption of glucose nutrients, but the generated H2O2 can be further used for other cancer therapies, such as gas therapy,5 metal-ion therapy,6 and chemodynamic therapy (CDT), Such multimodal treatment may induce a stronger therapeutic effect than that of each monotherapy, thus the cascade reaction will become a new trend of tumor treatment.

Recently, Huang Peng’s team from Shenzhen University published “Biodegradable Manganese-Doped Calcium Phosphate Nanotheranostics for Traceable Cascade Reaction-Enhanced Anti-Tumor Therapy”on ACS Nano, Herein, GOx is mineralized with manganese-doped calcium phosphate (MnCaP) to form spherical nanoparticles (GOx-MnCaP NPs) by an in situ biomimetic mineralization method, followed by the loading of doxorubicin (DOX) to construct a biodegradable, biocompatible, and tumor acidity-responsive nanotheranostics for magnetic resonance imaging (MRI) and cascade reaction-enhanced cooperative cancer treatment. The GOx-driven oxidation reaction can effectively eliminate intratumoral glucose for starvation therapy, and the elevated H2O2 is then converted into highly toxic hydroxyl radicals via a Mn²⁺-mediated Fenton-like reaction for chemodynamic therapy (CDT). Moreover, the acidity amplification due to the gluconic acid generation will in turn accelerate the degradation of the nanoplatform and promote the Mn²⁺H2O2 reaction for enhanced CDT. Meanwhile, the released Mn²⁺ ions can be used for MRI to monitor the treatment process.

DOI: 10.1021/acsnano.9b05836

周孟瑒