Bai Jing, Peng Chengjia, Guo Liping, Zhou Ming
Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Key Laboratory of Polyoxometalate Science of Ministry of Education, National & Local United Engineering Laboratory for Power Batteries, Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin 130024, People's Republic of China.
ACS Biomater Sci Eng. 2019 Nov 11;5(11):6207-6215. doi: 10.1021/acsbiomaterials.9b01200. Epub 2019 Nov 1.
Emerging natural-enzyme-based nanocatalytic tumor therapy depending on the high catalytic performance of natural enzymes has inspired great research interest in clinical applications. Nevertheless, the natural-enzyme-based catalytic therapy efficiency is seriously hampered by the low operational stability, poor delivery efficiency, and the short lifetime of enzymes. Herein, a bioreactor based on zeolitic imidazolate framework-8 (ZIF-8) was fabricated through one-pot embedding horseradish peroxidase (HRP) and glucose oxidase (Gox) strategy (ZIF-8@Gox/HRP) for synergistic cancer therapy. Notably, the obtained ZIF-8@Gox/HRP can efficiently consume endogenous glucose to generate gluconic acid and HO for starving tumors, and subsequently, HO was decomposed by encapsulated HRP to release high-toxic OH radicals, inducing cancer cell apoptosis for oxidation therapy. Importantly, in vivo results showed that ZIF-8@Gox/HRP had an impressive tumor-suppression rate based on cascade catalytic reaction. Therefore, this work paves a new avenue to design smart enzyme-based platforms for safe and efficient cancer therapy.
基于天然酶高催化性能的新兴天然酶基纳米催化肿瘤治疗激发了临床应用方面的巨大研究兴趣。然而，基于天然酶的催化治疗效率受到酶的低操作稳定性、低递送效率和短寿命的严重阻碍。在此，通过一锅法包埋辣根过氧化物酶（HRP）和葡萄糖氧化酶（Gox）策略（ZIF-8@Gox/HRP）制备了一种基于沸石咪唑酯骨架-8（ZIF-8）的生物反应器用于协同癌症治疗。值得注意的是，所获得的ZIF-8@Gox/HRP可以有效消耗内源性葡萄糖以产生葡萄糖酸和H₂O₂来饿死肿瘤，随后，封装的HRP将H₂O₂分解以释放高毒性的·OH自由基，诱导癌细胞凋亡以进行氧化治疗。重要的是，体内结果表明ZIF-8@Gox/HRP基于级联催化反应具有令人印象深刻的肿瘤抑制率。因此，这项工作为设计用于安全高效癌症治疗的智能酶基平台开辟了一条新途径。
