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Author: Sophia
Summary: Nanozyme-catalyzed therapy has become one of the hot topics in cancer treatment, and its therapeutic effect is highly correlated with its catalytic efficiency.
2023年12月31日，四川大学华西医院罗奎团队在期刊《Advanced Science》上发表题为“Unraveling Ros Conversion Through Enhanced Enzyme-Like Activity with Copper-Doped Cerium Oxide for Tumor Nanocatalytic Therapy”的研究论文，研究表明线状CeO2/Cu纳米颗粒作为人工酶体系，在癌细胞细胞内ROS的干预中具有巨大潜力，可实现有效的纳米催化治疗。
https://onlinelibrary.wiley.com/doi/10.1002/advs.202307154
Background:
01
Despite the development of multiple anti-cancer strategies, chemotherapy remains an indispensable treatment for the treatment of different malignancies. Nanozyme-catalyzed therapy is an emerging chemotherapy method. Nanozymes are nanomaterials with enzyme mimicry properties, which have the advantages of higher stability, higher cost-effectiveness, and less stringent storage conditions than natural enzymes, so they are attracting more and more attention. In particular, nanozymes, combined with their unique properties and catalytic capabilities, have great potential in a variety of applications, from in vitro diagnostics to alternative use in certain biological systems. Nanozymes have been explored to treat cancer by regulating intracellular reactive oxygen species (ROS).
ROS has an important function in regulating various physiological functions and is therefore essential for living organisms. The intrinsic biochemical properties of ROS can prove the mechanism of physiological activities of organisms and deserve in-depth study. In cancer cells, intracellular electron transport chains and NADPH oxidase lead to the sustained production of O2∙−. O2∙- is stably converted to H2O2 under superoxide dismutase (SOD) catalyze, and further converted to hydroxyl radicals by peroxidase-like (POD) reactions. In order to improve the catalytic ability of nanozymes, Ir-N5 SA/Cer was prepared by introducing axial N coordination in SA enzymes. Ir-N5 SA has been reported to activate natural oxidases, peroxidases, and catalases, as well as catalyze NAHD to H2O2. However, it is challenging to promote ∙OH production through intracellular SOD and POD, therefore, various methods have been tried to continuously produce ∙OH within cancer cells to enhance the cytotoxicity of ROS for antitumor therapy. For example, nanozymes can be developed to continuously convert endogenous ROS (O2∙− and H2O2) within cancer cells to ∙OH.
Research Progress
02
CeO2 has sufficient surface oxygen vacancies, which are essential for O2∙− hydrogenation and H2O2 decomposition. CeO2 has morphology with different exposed crystal planes and has been found to be essential in a range of reactions. Here, we fabricated CeO2 of wire (CeO2/Cu-W), cube (CeO2/Cu-C) and octahedral (CeO2/Cu-O) as supports for copper metal. Compared with CeO2/Cu-C and CeO2/Cu-O, CeO2/Cu-W exhibited higher SOD and POD activities, and promoted the continuous catalysis of O2∙−→H2O2→∙OH in cancer cells through the relay reaction supported by oxygen vacancies, and finally achieved the continuous production of ∙OH and triggered apoptosis of cancer cells (Fig. 1).
CeO2/Cu mediates the mechanism of O2∙-→H2O2→OH relay transformation to induce cancer cell death.
Conclusions of the study
03
In this study, CeO2/Cu was reported as a biomimetic SOD that converts O2∙- to H2O2 and peroxidase (POD) → to achieve H2O2 →∙OH. Importantly, CeO2/Cu artificial enzymes with linear shapes promote direct alterations of endogenous ROS to the target molecule (∙OH). In particular, it can be applied to the intervention of ROS in cancer cells. Linear CeO2/Cu nanoparticles have excellent SOD-like and POD-like catalytic efficiency, showing the best anti-tumor effect and improving the efficiency of anti-tumor drugs. This study provides a promising strategy for manipulating oxygen vacancy formation and structural shape of catalytic inorganic nanoparticles to regulate intracellular ROS levels.
Resources:
https://onlinelibrary.wiley.com/doi/10.1002/advs.202307154
Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment options. If you need health guidance, please visit a regular hospital.
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