Chen Li, Zhao Lu, Hu Guoyang, Jin Ronghua, Cai Bolei, Bai Yongkang, Chen Xin
Department of Chemical Engineering, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, School of Chemical Engineering and Technology, Xi'an Jiao Tong University, Xi'an, 710049, China.
J Mater Chem B. 2020 Aug 21;8(31):6857-6865. doi: 10.1039/c9tb02812a. Epub 2020 Feb 5.
Catalytic medicine based on various catalysts has attracted increasing interest for the treatment of tumors. However, the direct application of conventional catalysts may cause serious side effects to healthy tissue and low therapeutic efficiency against tumor tissue, due to their weak specificity for the tumor microenvironment (TME). Herein, a tumor-targeting and TME-responsive nanoreactor containing ferroferric oxide nanoparticles (FeO NPs) and glucose oxidase (GOD) was developed to perform hyaluronidase (HAase) and glutathione (GSH)-triggered chain catalytic reactions in tumor tissue. This nanoreactor was designed to take advantage of the unique biological molecules in tumors and several therapeutic agents to adjust the local microenvironments, and achieved satisfactory and accurate tumor therapy. The reactions started with the consumption of intratumoral glucose to inhibit tumor growth, and simultaneously produced hydrogen peroxide (HO) to make up for the deficiency of HO in the original tumor microenvironment, resulting in the generation of a high quantity of hydroxyl radicals as a result of the catalysis of FeO NPs to further eliminate tumor tissue. The tumor-specific catalytic medicine formed by our nanocomposite guaranteed both therapeutic efficiency and accuracy, avoiding potential risks to healthy tissue and leading to a four-fold improvement in the cytotoxicity against tumor cells compared with normal cells after incubations of 48 h. In vivo data from mouse models provided further evidence for its therapeutic efficacy: the tumor growth was completely inhibited after two weeks of the synergistic therapy, which indicated the promise of our nanocomposite for tumor treatment.
基于各种催化剂的催化医学在肿瘤治疗方面引起了越来越多的关注。然而，由于传统催化剂对肿瘤微环境（TME）的特异性较弱，其直接应用可能会对健康组织造成严重副作用，且对肿瘤组织的治疗效率较低。在此，我们开发了一种含有四氧化三铁纳米颗粒（FeO NPs）和葡萄糖氧化酶（GOD）的肿瘤靶向且TME响应性纳米反应器，以在肿瘤组织中进行透明质酸酶（HAase）和谷胱甘肽（GSH）触发的链式催化反应。该纳米反应器旨在利用肿瘤中独特的生物分子和多种治疗剂来调节局部微环境，并实现了令人满意且精确的肿瘤治疗。反应首先通过消耗肿瘤内的葡萄糖来抑制肿瘤生长，同时产生过氧化氢（HO）以弥补原始肿瘤微环境中HO的不足，由于FeO NPs的催化作用，导致产生大量羟基自由基以进一步消除肿瘤组织。我们的纳米复合材料形成的肿瘤特异性催化药物保证了治疗效率和准确性，避免了对健康组织的潜在风险，并且在孵育48小时后，与正常细胞相比，对肿瘤细胞的细胞毒性提高了四倍。来自小鼠模型的体内数据进一步证明了其治疗效果：协同治疗两周后肿瘤生长完全受到抑制，这表明我们的纳米复合材料在肿瘤治疗方面具有潜力。
