Guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy
Clinical applications of nanozyme-initiated chemodynamic therapy (NCDT) have been severely limited by poor catalytic efficiency of nanozymes, insufficient endogenous H2O2 content, and off-target consumption. Herein, we develop hollow mesoporous Mn/Zr-co-doped CeO2 tandem nanozyme (PHMZCO-AT) with el...
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sg-ntu-dr.10356-1559402023-02-28T19:27:02Z Guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy Dong, Shuming Dong, Yushan Liu, Bin Liu, Jing Liu, Shikai Zhao, Zhiyu Li, Wenting Tian, Boshi Zhao, Ruoxi He, Fei Gai, Shili Xie, Ying Yang, Piaoping Zhao, Yanli School of Physical and Mathematical Sciences Science::Chemistry Cancer Treatment Chemodynamic Therapy Clinical applications of nanozyme-initiated chemodynamic therapy (NCDT) have been severely limited by poor catalytic efficiency of nanozymes, insufficient endogenous H2O2 content, and off-target consumption. Herein, we develop hollow mesoporous Mn/Zr-co-doped CeO2 tandem nanozyme (PHMZCO-AT) with elaborately regulated multi-enzymatic activities, i.e., simultaneously enhancing superoxide dismutase (SOD)-like and peroxidase (POD)-like activities and inhibiting catalase (CAT)-like activity, serving as an H2O2 homeostasis disruptor to promote H2O2 evolvement and restrain off-target elimination of H2O2 for achieving intensive NCDT. PHMZCO-AT nanozymes with SOD-like activity can catalyze endogenous O2·– into H2O2 in the tumor region. The suppression of CAT activity and depletion of glutathione by PHMZCO-AT largely weaken the off-target decomposition of H2O2 to H2O. Elevated H2O2 is then exclusively catalyzed by the downstream POD-like activity of PHMZCO-AT to generate toxic hydroxyl radicals, further inducing tumor apoptosis and death. T1-weighted magnetic resonance imaging and high-contrast X-ray computed tomography imaging are also achieved using PEG/PHMZCO-AT nanozymes due to the existence of paramagnetic Mn2+ species and high X-ray attenuation ability of elemental Zr, permitting in vivo tracking of the therapeutic process. This work presents a powerful paradigm to achieve intensive NCDT efficacy by simultaneously regulating multi-enzymatic activities of Ce-based nanozymes and perturbing the H2O2 homeostasis in tumor microenvironment. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Submitted/Accepted version The work was supported by the MOST Grant (2016YFA0101202), the National Natural Science Foundation of China (51972075 and 51772059), the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081), the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03), and the Fundamental Research Funds for the Central Universities. 2022-03-25T07:50:59Z 2022-03-25T07:50:59Z 2022 Journal Article Dong, S., Dong, Y., Liu, B., Liu, J., Liu, S., Zhao, Z., Li, W., Tian, B., Zhao, R., He, F., Gai, S., Xie, Y., Yang, P. & Zhao, Y. (2022). Guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy. Advanced Materials, 34(7), 2107054-. https://dx.doi.org/10.1002/adma.202107054 0935-9648 https://hdl.handle.net/10356/155940 10.1002/adma.202107054 7 34 2107054 en A20E5c0081 NRF-NRFI2018-03 Advanced Materials This is the peer reviewed version of the following article: Dong, S., Dong, Y., Liu, B., Liu, J., Liu, S., Zhao, Z., Li, W., Tian, B., Zhao, R., He, F., Gai, S., Xie, Y., Yang, P. & Zhao, Y. (2022). Guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy. Advanced Materials, 34(7), 2107054, which has been published in final form at https://doi.org/10.1002/adma.202107054. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. application/pdf |
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Science::Chemistry Cancer Treatment Chemodynamic Therapy Dong, Shuming Dong, Yushan Liu, Bin Liu, Jing Liu, Shikai Zhao, Zhiyu Li, Wenting Tian, Boshi Zhao, Ruoxi He, Fei Gai, Shili Xie, Ying Yang, Piaoping Zhao, Yanli Guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy |
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Clinical applications of nanozyme-initiated chemodynamic therapy (NCDT) have been severely limited by poor catalytic efficiency of nanozymes, insufficient endogenous H2O2 content, and off-target consumption. Herein, we develop hollow mesoporous Mn/Zr-co-doped CeO2 tandem nanozyme (PHMZCO-AT) with elaborately regulated multi-enzymatic activities, i.e., simultaneously enhancing superoxide dismutase (SOD)-like and peroxidase (POD)-like activities and inhibiting catalase (CAT)-like activity, serving as an H2O2 homeostasis disruptor to promote H2O2 evolvement and restrain off-target elimination of H2O2 for achieving intensive NCDT. PHMZCO-AT nanozymes with SOD-like activity can catalyze endogenous O2·– into H2O2 in the tumor region. The suppression of CAT activity and depletion of glutathione by PHMZCO-AT largely weaken the off-target decomposition of H2O2 to H2O. Elevated H2O2 is then exclusively catalyzed by the downstream POD-like activity of PHMZCO-AT to generate toxic hydroxyl radicals, further inducing tumor apoptosis and death. T1-weighted magnetic resonance imaging and high-contrast X-ray computed tomography imaging are also achieved using PEG/PHMZCO-AT nanozymes due to the existence of paramagnetic Mn2+ species and high X-ray attenuation ability of elemental Zr, permitting in vivo tracking of the therapeutic process. This work presents a powerful paradigm to achieve intensive NCDT efficacy by simultaneously regulating multi-enzymatic activities of Ce-based nanozymes and perturbing the H2O2 homeostasis in tumor microenvironment. |
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School of Physical and Mathematical Sciences |
author_facet |
School of Physical and Mathematical Sciences Dong, Shuming Dong, Yushan Liu, Bin Liu, Jing Liu, Shikai Zhao, Zhiyu Li, Wenting Tian, Boshi Zhao, Ruoxi He, Fei Gai, Shili Xie, Ying Yang, Piaoping Zhao, Yanli |
format |
Article |
author |
Dong, Shuming Dong, Yushan Liu, Bin Liu, Jing Liu, Shikai Zhao, Zhiyu Li, Wenting Tian, Boshi Zhao, Ruoxi He, Fei Gai, Shili Xie, Ying Yang, Piaoping Zhao, Yanli |
author_sort |
Dong, Shuming |
title |
Guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy |
title_short |
Guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy |
title_full |
Guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy |
title_fullStr |
Guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy |
title_full_unstemmed |
Guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy |
title_sort |
guiding transition metal-doped hollow cerium tandem nanozymes with elaborately regulated multi-enzymatic activities for intensive chemodynamic therapy |
publishDate |
2022 |
url |
https://hdl.handle.net/10356/155940 |
_version_ |
1759858191760359424 |