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A multifunctional cascade bioreactor based on a layered double oxides composite hydrogel for synergetic tumor chemodynamic/starvation/photothermal therapy

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机构： [1]School of Materials Science and Engineering, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China [2]State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China [3]Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China [4]Intervention Center, Eastern Hepatobiliary Surgery Hospital, the Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China [5]Department of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China [6]School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan,Hangzhou 310024, China

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The field of nanomedicine-catalyzed tumor therapy has achieved a lot of progress; however, overcoming the limitations of the tumor microenvironment (TME) to achieve the desired therapeutic effect remains a major challenge. In this study, a nanocomposite hydrogel (GH@LDO) platform combining the nanozyme CoMnFe-layered double oxides (CoMnFe-LDO) and natural enzyme glucose oxidase (GOX) was engineered to remodel the TME to enhance tumor catalytic therapy. The CoMnFe-LDO is a nanozyme that can convert endogenous H2O2 into reactive oxygen species (ROS) and O2 to achieve chemodynamic therapy (CDT) and alleviate the hypoxic microenvironment. Meanwhile, GOX can catalyze the conversion of glucose and O2 to gluconic acid and H2O2, which not only represses the ATP production of tumor cells to achieve starvation therapy (ST), but also decreases the pH value of TME and supplies extra H2O2 to enhance the CDT effect. Furthermore, this well-designed CoMnFe-LDO possessed a high photothermal conversion efficiency of GH@LDO (66.63%), which could promote the generation of ROS to enhance the CDT effect and achieve photothermal therapy (PTT) under near-infrared light irradiation. The GH@LDO hydrogel performes cascade reaction which overcomes the limitation of the TME and achieves satisfactory CDT/ST/PTT synergetic effects in vitro and in vivo. This work provides a new strategy for remodeling the TME using nanomedicine to achieve precise tumor cascaded catalytic therapy. STATEMENT OF SIGNIFICANCE: At present, the focus of tumor therapy has begun to shift from monotherapy to combination therapy for improving the overall therapeutic effect. In this study, we synthesized a CoMnFe-LDO nanozyme composed of multiple transition metal oxides, which demonstrated improved peroxidase and oxidase activities as well as favorable photothermal conversion capability. The CoMnFe-LDO nanozyme was compounded with an injectable GH hydrogel crosslinked by GOX and horseradish peroxidase (HRP). This nanocomposite hydrogel overcame the limitations of weak acidity, H2O2, and O2 levels in the TME and achieved synergetic CDT, ST, and PTT effects based on the cascaded catalytic actions of CoMnFe-LDO and GOX to H2O2 and glucose.Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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出版当年[2021]版：

大类 | 1 区

工程技术

小类 | 1 区工程：生物医学 1 区材料科学：生物材料

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区工程：生物医学 1 区材料科学：生物材料

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出版当年[2020]版：

Q1 MATERIALS SCIENCE, BIOMATERIALS Q1 ENGINEERING, BIOMEDICAL

最新[2023]版：

Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子： 9.4 最新[2023版] 9.9 最新五年平均 8.947 出版当年[2020版] 9 出版当年五年平均 7.242 出版前一年[2019版] 10.633 出版后一年[2021版]

第一作者：

第一作者机构： [1]School of Materials Science and Engineering, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China [2]State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China

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通讯作者：

通讯机构： [2]State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China [3]Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China [6]School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan,Hangzhou 310024, China [*1]State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.

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