Naganuma Tamaki
Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
Biomater Sci. 2021 Feb 23;9(4):1345-1354. doi: 10.1039/d0bm01860k.
Switching of the Ce3+/Ce4+ oxidation states in cerium oxide nanoparticles (CNPs) provides various superior nanozyme activities. However, nanozymes lack a switch to reversibly regulate the multi-nanozyme capacity depending on physiological/pathological environments, e.g. different pH and H2O2 levels. Furthermore, highly concentrated Ce3+ ions with abundant oxygen vacancies (Vo) in CNPs have the potential to enhance their catalytic activities, but the phosphate anions (P) adsorbed on Ce3+ ions block their several catalytic activities. This study, therefore, demonstrates that the tunable P-mediated stability of Ce3+ ions involves the superoxide dismutase (SOD) mimetic activity of CNPs, and leads to enhanced switching efficiency of their anti/pro-oxidant activities. Herein, highly concentrated Ce3+ ions in Vo-CNP layers (Vo-CNPLs) were fabricated, and the threshold conditions necessary to alter the stability of Ce3+ ions treated with P were explored by X-ray photoelectron spectroscopy. P-adsorbed Ce3+ ions (P-Ce3+) in Vo-CNPLs were efficiently destabilized in H2O2 solution (pH 5-6) rather than in HCl and HNO3 solutions (pH 3), and the presence of H2O2 readily released P from Ce3+ sites. Indeed, though P-Ce3+ temporarily arrested the SOD mimetic activity to generate H2O2 (linked to anti-oxidant activity) at physiological pH, they did enable the initiation of SOD mimetic activity (pro-oxidant activity) even at pH 5 close to biologically-appropriate acid conditions, e.g. in lysosome/endosome/tumor-microenvironments. These findings suggest that P-Ce3+ ions enhance the switching efficiency of their anti/pro-oxidant activities. Thus, P-mediated switches could be utilized to achieve a better understanding of the nanozyme switching-mechanisms, and for the design of multi-functional nanozymes for enhancing therapeutic efficacy.
氧化铈纳米颗粒（CNPs）中Ce3+/Ce4+氧化态的转换具有多种优异的纳米酶活性。然而，纳米酶缺乏一种能够根据生理/病理环境（例如不同的pH值和过氧化氢水平）可逆调节其多纳米酶活性的开关。此外，CNPs中具有大量氧空位（Vo）的高浓度Ce3+离子有可能增强其催化活性，但吸附在Ce3+离子上的磷酸根阴离子（P）会阻碍其多种催化活性。因此，本研究表明，P介导的Ce3+离子可调稳定性涉及CNPs的超氧化物歧化酶（SOD）模拟活性，并提高了其抗氧化/促氧化活性的转换效率。在此，制备了Vo-CNP层（Vo-CNPLs）中的高浓度Ce3+离子，并通过X射线光电子能谱探索了改变P处理的Ce3+离子稳定性所需的阈值条件。Vo-CNPLs中吸附P的Ce3+离子（P-Ce3+）在过氧化氢溶液（pH 5-6）中比在HCl和HNO3溶液（pH 3）中更有效地去稳定，并且过氧化氢的存在很容易从Ce3+位点释放P。事实上，尽管P-Ce3+在生理pH值下暂时抑制了产生过氧化氢（与抗氧化活性相关）的SOD模拟活性，但它们即使在接近生物适宜酸性条件（例如在溶酶体/内体/肿瘤微环境中）的pH 5下也能启动SOD模拟活性（促氧化活性）。这些发现表明，P-Ce3+离子提高了其抗氧化/促氧化活性的转换效率。因此，P介导的开关可用于更好地理解纳米酶的转换机制，并用于设计增强治疗效果的多功能纳米酶。
