Chen Daomei, Jiang Liang, Lei Tao, Xiao Guo, Wang Yuanfeng, Zuo Xiaoqiong, Li Bin, Li Lingli, Wang Jiaqiang
National Center for International Research on Photoelectric and Energy Materials, School of Materials and Energy, Yunnan University, Kunming 650091, P R China.
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan University, Kunming 650091, P R China.
Biomater Biosyst. 2022 Jan 5;5:100038. doi: 10.1016/j.bbiosy.2021.100038. eCollection 2022 Mar.
Protease has been widely used in biological and industrial fields. Developing efficient artificial enzyme mimics remains a major technical challenge due to the high stability of peptide bonds. Nanoenzymes with high stability, high activity and low cost, provided new opportunities to break through natural enzyme inherent limitations. However, compared with many nanomaterials with inherent peroxidase activity, the intrinsic mimic proteases properties of magnetic nanomaterials were seldom explored, let alone the interaction between magnetic nanomaterials and cellular proteins. Herein, we reported for the first time that magnetic CuFeO possesses inherent protease activity to hydrolyze bovine serum albumin (BSA) and casein under physiological conditions, and the CuFeO is more resistant to high temperature than the natural trypsin. It also exhibited significantly higher catalytic efficiency than other copper nanomaterials and can be recycled for many times. Protease participated in pathophysiological processes and all stages of tumor progression. Interesting, CuFeO exhibited anti-proliferative effect on A549, SKOV3, HT-29, BABL-3T3 and HUVEC cells, as well as it was particularly sensitive against SKOV3 cells. CuFeO was about 30 times more effective than conventional chemotherapy drugs oxaliplatin and artesunate against SKOV3 cells. In addition, CuFeO also mediated the expression of intracellular proteins, such as MMP-2, MMP-9, F-actin, and NF-B, which may be associated with global protein hydrolysis by CuFeO, leading to inhibition of cell migration. The merits of the high magnetic properties, good protease-mimic and antitumor activities make CuFeO nanoparticles very prospective candidates for many applications such as proteomics and biotechnology.
蛋白酶已在生物和工业领域中广泛应用。由于肽键的高稳定性，开发高效的人工酶模拟物仍然是一项重大技术挑战。具有高稳定性、高活性和低成本的纳米酶为突破天然酶的固有局限性提供了新机遇。然而，与许多具有固有过氧化物酶活性的纳米材料相比，磁性纳米材料的固有模拟蛋白酶特性很少被探索，更不用说磁性纳米材料与细胞蛋白之间的相互作用了。在此，我们首次报道磁性 CuFeO 在生理条件下具有水解牛血清白蛋白（BSA）和酪蛋白的固有蛋白酶活性，并且 CuFeO 比天然胰蛋白酶更耐高温。它还表现出比其他铜纳米材料显著更高的催化效率，并且可以多次循环使用。蛋白酶参与病理生理过程以及肿瘤进展的各个阶段。有趣的是，CuFeO 对 A549、SKOV3、HT - 29、BABL - 3T3 和 HUVEC 细胞具有抗增殖作用，并且对 SKOV3 细胞特别敏感。CuFeO 对 SKOV3 细胞的有效性比传统化疗药物奥沙利铂和青蒿琥酯高约 30 倍。此外，CuFeO 还介导细胞内蛋白如 MMP - 2、MMP - 9、F - 肌动蛋白和核因子κB 的表达，这可能与 CuFeO 介导的整体蛋白水解有关，导致细胞迁移受到抑制。高磁性特性、良好的模拟蛋白酶和抗肿瘤活性等优点使 CuFeO 纳米颗粒在蛋白质组学和生物技术等许多应用中成为非常有前景的候选材料。
