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Chemodynamic therapy (CDT) based on cascade catalytic nanomedicine has emerged as a promising cancer treatment strategy. However, most of the reported cascade catalytic systems are designed based on symmetric- or co-assembly of multiple catalytic active sites, in which their functions are difficult to perform independently and may interfere with each other. Especially in cascade catalytic system that involves fragile natural-enzymes, the strong oxidation of free-radicals toward natural-enzymes should be carefully considered, and the spatial distribution of the multiple catalytic active sites should be carefully organized to avoid the degradation of the enzyme catalytic activity. Herein, a spatially-asymmetric cascade nanocatalyst is developed for enhanced CDT, which is composed by a Fe3O4 head and a closely connected mesoporous silica nanorod immobilized with glucose oxidase (mSiO2-GOx). The mSiO2-GOx subunit could effectively deplete glucose in tumor cells, and meanwhile produce a considerable amount of H2O2 for subsequent Fenton reaction under the catalysis of Fe3O4 subunit in the tumor microenvironment. Taking the advantage of the spatial isolation of mSiO2-GOx and Fe3O4 subunits, the catalysis of GOx and free-radicals generation occur at different domains of the asymmetric nanocomposite, minimizing the strong oxidation of free-radicals toward the activity of GOx at the other side. In addition, direct exposure of Fe3O4 subunit without any shelter could further enhance the strong oxidation of free-radicals toward objectives. So, compared with traditional core@shell structure, the long-term stability and efficiency of the asymmetric cascade catalytic for CDT is greatly increased by 138%, thus realizing improved cancer cell killing and tumor restrain efficiency.
Lin, H.; Chen, Y.; Shi, J. L. Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy. Chem. Soc. Rev. 2018, 47, 1938–1958.
Fan, Y.; Liu, S. E.; Yi, Y.; Rong, H. P.; Zhang, J. T. Catalytic nanomaterials toward atomic levels for biomedical applications: From metal clusters to single-atom catalysts. ACS Nano 2021, 15, 2005–2037.
Tong, Z. R.; Gao, Y.; Yang, H.; Wang, W. L.; Mao, Z. W. Nanomaterials for cascade promoted catalytic cancer therapy. View 2021, 2, 20200133.
Ding, Y.; Xu, H.; Xu, C.; Tong, Z. R.; Zhang, S. T.; Bai, Y.; Chen, Y. N.; Xu, Q. H.; Zhou, L. Z.; Ding, H. et al. A nanomedicine fabricated from gold nanoparticles-decorated metal-organic framework for cascade chemo/chemodynamic cancer therapy. Adv Sci. 2020, 7, 2001060.
Chen, W. T.; Ding, S. S.; Wu, J. R.; Shi, G. Y.; Zhu, A. W. In situ detection of hydroxyl radicals in mitochondrial oxidative stress with a nanopipette electrode. Chem. Commun. 2020, 56, 13225–13228.
Sang, Y. J.; Li, W.; Liu, H.; Zhang, L.; Wang, H.; Liu, Z. W.; Ren, J. S.; Qu, X. G. Construction of nanozyme-hydrogel for enhanced capture and elimination of bacteria. Adv. Funct. Mater. 2019, 29, 1900518.
Pryor, W. A. Oxy-radicals and related species: Their formation, lifetimes, and reactions. Annu. Rev. Physiol. 1986, 48, 657–667.
Hatz, S.; Lambert, J. D. C.; Ogilby, P. R. Measuring the lifetime of singlet oxygen in a single cell: Addressing the issue of cell viability. Photochem. Photobiol. Sci. 2007, 6, 1106–1116.
Srinivas, U. S.; Tan, B. W. Q.; Vellayappan, B. A.; Jeyasekharan, A. D. ROS and the DNA damage response in cancer. Redox Biol. 2019, 25, 101084.
Halliwell, B.; Adhikary, A.; Dingfelder, M.; Dizdaroglu, M. Hydroxyl radical is a significant player in oxidative DNA damage in vivo. Chem. Soc. Rev. 2021, 50, 8355–8360.
Yan, L. L.; Zaher, H. S. How do cells cope with RNA damage and its consequences? J. Biol. Chem. 2019, 294, 15158–15171.
Fei, W. D.; Chen, D. F.; Tang, H. X.; Li, C. Q.; Zheng, W. Z.; Chen, F. Y.; Song, Q. Q.; Zhao, Y. C.; Zou, Y.; Zheng, C. H. Targeted GSH-exhausting and hydroxyl radical self-producing manganese-silica nanomissiles for MRI guided ferroptotic cancer therapy. Nanoscale 2020, 12, 16738–16754.
Song, C.; Ouyang, Z. J.; Gao, Y.; Guo, H. H.; Wang, S. J.; Wang, D. Y.; Xia, J. D.; Shen, M. W.; Shi, X. Y. Modular design of multifunctional core-shell tecto dendrimers complexed with copper(II) for MR imaging-guided chemodynamic therapy of orthotopic glioma. Nano Today 2021, 41, 101325.
Guptasarma, P.; Balasubramanian, D.; Matsugo, S.; Saito, I. Hydroxyl radical mediated damage to proteins, with special reference to the crystallins. Biochemistry 1992, 31, 4296–4303.
Circu, M. L.; Aw, T. Y. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic. Biol. Med. 2010, 48, 749–762.
Cadet, J.; Davies, K. J. A.; Medeiros, M. H. G.; Di Mascio, P.; Wagner, J. R. Formation and repair of oxidatively generated damage in cellular DNA. Free Radic. Biol. Med. 2017, 107, 13–34.
Zhang, L.; Wan, S. S.; Li, C. X.; Xu, L.; Cheng, H.; Zhang, X. Z. An adenosine triphosphate-responsive autocatalytic Fenton nanoparticle for tumor ablation with self-supplied H2O2 and acceleration of Fe(III)/Fe(II) conversion. Nano Lett. 2018, 18, 7609–7618.
Zhang, S. C.; Cao, C. Y.; Lv, X. Y.; Dai, H. M.; Zhong, Z. H.; Liang, C.; Wang, W. J.; Huang, W.; Song, X. J.; Dong, X. C. A H2O2 Self-sufficient nanoplatform with domino effects for thermal-responsive enhanced chemodynamic therapy. Chem. Sci. 2020, 11, 1926–1934.
Tang, Z.; Liu, Y.; He, M.; Bu, W. Chemodynamic therapy: tumour microenvironment-mediated Fenton and Fenton-like reactions. Angew. Chem. Int. Ed. 2019, 58, 946–956.
Chen, Q.; Feng, L. Z.; Liu, J. J.; Zhu, W. W.; Dong, Z. L.; Wu, Y. F.; Liu, Z. Intelligent albumin-MnO2 nanoparticles as pH-/H2O2-responsive dissociable nanocarriers to modulate tumor hypoxia for effective combination therapy. Adv. Mater. 2016, 28, 7129–7136.
Szatrowski, T. P.; Nathan, C. F. Production of large amounts of hydrogen peroxide by human tumor Cells. Cancer Res. 1991, 51, 794–798.
Wang, M.; Wang, D. M.; Chen, Q.; Li, C. X.; Li, Z. Q.; Lin, J. Recent advances in glucose-oxidase-based nanocomposites for tumor therapy. Small 2019, 15, 1903895.
Fu, L. H.; Qi, C.; Hu, Y. R.; Lin, J.; Huang, P. Glucose oxidase-instructed multimodal synergistic cancer therapy. Adv. Mater. 2019, 31, 1808325.
Chang, M. Y.; Wang, M.; Wang, M. F.; Shu, M. M.; Ding, B. B.; Li, C. X.; Pang, M. L.; Cui, S. Z.; Hou, Z. Y.; Lin, J. A multifunctional cascade bioreactor based on hollow-structured Cu2MoS4 for synergetic cancer chemo-dynamic therapy/starvation therapy/phototherapy/immunotherapy with remarkably enhanced efficacy. Adv. Mater. 2019, 31, 1905271.
Wang, T. T.; Zhang, H.; Liu, H. H.; Yuan, Q.; Ren, F.; Han, Y. B.; Sun, Q.; Li, Z.; Gao, M. Y. Boosting H2O2-guided chemodynamic therapy of cancer by enhancing reaction kinetics through versatile biomimetic Fenton nanocatalysts and the second near-infrared light irradiation. Adv. Funct. Mater. 2020, 30, 1906128.
Fu, L. H.; Hu, Y. R.; Qi, C.; He, T.; Jiang, S. S.; Jiang, C.; He, J.; Qu, J. L.; Lin, J.; Huang, P. Biodegradable manganese-doped calcium phosphate nanotheranostics for traceable cascade reaction-enhanced anti-tumor therapy. ACS Nano 2019, 13, 13985–13994.
Wang, C. H.; Yang, J. X.; Dong, C. Y.; Shi, S. Glucose oxidase-related cancer therapies. Adv. Therap. 2020, 3, 2000110.
Huo, M. F.; Wang, L. Y.; Chen, Y.; Shi, J. L. Tumor-selective catalytic nanomedicine by nanocatalyst delivery. Nat. Commun. 2017, 8, 357.
Feng, W.; Han, X. G.; Wang, R. Y.; Gao, X.; Hu, P.; Yue, W. W.; Chen, Y.; Shi, J. L. Nanocatalysts-augmented and photothermal-enhanced tumor-specific sequential nanocatalytic therapy in both NIR-I and NIR-II biowindows. Adv. Mater. 2019, 31, 1805919.
Chang, K. W.; Liu, Z. H.; Fang, X. F.; Chen, H. B.; Men, X. J.; Yuan, Y.; Sun, K.; Zhang, X. J.; Yuan, Z.; Wu, C. F. Enhanced phototherapy by nanoparticle-enzyme via generation and photolysis of hydrogen peroxide. Nano Lett. 2017, 17, 4323–4329.
Feng, L. L.; Xie, R.; Wang, C. Q.; Gai, S. L.; He, F.; Yang, D.; Yang, P. P.; Lin, J. Magnetic targeting, tumor microenvironment-responsive intelligent nanocatalysts for enhanced tumor ablation. ACS Nano 2018, 12, 11000–11012.
Yang, X.; Yang, Y.; Gao, F.; Wei, J. J.; Qian, C. G.; Sun, M. J. Biomimetic hybrid nanozymes with self-supplied H+ and accelerated O2 generation for enhanced starvation and photodynamic therapy against hypoxic tumors. Nano Lett. 2019, 19, 4334–4342.
Zhao, T. C.; Zhu, X. H.; Hung, C. T.; Wang, P. Y.; Elzatahry, A.; Al-Khalaf, A. A.; Hozzein, W. N.; Zhang, F.; Li, X. M.; Zhao, D. Y. Spatial isolation of carbon and silica in a single Janus mesoporous nanoparticle with tunable amphiphilicity. J. Am. Chem. Soc. 2018, 140, 10009–10015.
Zhang, L.; Zhang, F.; Dong, W. F.; Song, J. F.; Huo, Q. S.; Sun, H. B. Magnetic-mesoporous Janus nanoparticles. Chem. Commun. 2011, 47, 1225–1227.
Gao, L. Z.; Zhuang, J.; Nie, L.; Zhang, J. B.; Zhang, Y.; Gu, N.; Wang, T. H.; Feng, J.; Yang, D. L.; Perrett, S. et al. Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat. Nanotechnol. 2007, 2, 577–583.
Liu, J.; Sun, Z. K.; Deng, Y. H.; Zou, Y.; Li, C. Y.; Guo, X. H.; Xiong, L. Q.; Gao, Y.; Li, F. Y.; Zhao, D. Y. Highly water-dispersible biocompatible magnetite particles with low cytotoxicity stabilized by citrate groups. Angew. Chem., Int. Ed. 2009, 48, 5875–5879.
Zhao, T. C.; Chen, L.; Wang, P. Y.; Li, B. H.; Lin, R. F.; Al-Khalaf, A. A.; Hozzein, W. N.; Zhang, F.; Li, X. M.; Zhao, D. Y. Surface-kinetics mediated mesoporous multipods for enhanced bacterial adhesion and inhibition. Nat. Commun. 2019, 10, 4387.
Yu, Z. Z.; Zhou, P.; Pan, W.; Li, N.; Tang, B. A biomimetic nanoreactor for synergistic chemiexcited photodynamic therapy and starvation therapy against tumor metastasis. Nat. Commun. 2018, 9, 5044.
Sun, X. L.; Guo, S. J.; Chung, C. S.; Zhu, W. L.; Sun, S. H. A sensitive H2O2 assay based on dumbbell-like PtPd-Fe3O4 nanoparticles. Adv. Mater. 2013, 25, 132–136.
Gao, S. S.; Lin, H.; Zhang, H. X.; Yao, H. L.; Chen, Y.; Shi, J. L. Nanocatalytic tumor therapy by biomimetic dual inorganic nanozyme-catalyzed cascade reaction. Adv. Sci. 2019, 6, 1801733.
Nascimento, R. A. S.; Özel, R. E.; Mak, W. H.; Mulato, M.; Singaram, B.; Pourmand, N. Single cell “glucose nanosensor” verifies elevated glucose levels in individual cancer cells. Nano Lett. 2016, 16, 1194–1200.
Chen, Q. Q.; Yang, D. Y.; Yu, L. D.; Jing, X. X.; Chen, Y. Catalytic chemistry of iron-free Fenton nanocatalysts for versatile radical nanotherapeutics. Mater. Horiz. 2020, 7, 317–337.
Chen, J.; Wang, X. B.; Liu, Y. B.; Liu, H. L.; Gao, F. L.; Lan, C.; Yang, B. C.; Zhang, S. R.; Gao, Y. J. pH-responsive catalytic mesocrystals for chemodynamic therapy via ultrasound-assisted Fenton reaction. Chem. Eng. J. 2019, 369, 394–402.
Fu, L. H.; Qi, C.; Lin, J.; Huang, P. Catalytic chemistry of glucose oxidase in cancer diagnosis and treatment. Chem. Soc. Rev. 2018, 47, 6454–6472.
Lei, S.; Zhang, J.; Blum, N. T.; Li, M.; Zhang, D. Y.; Yin, W. M.; Zhao, F.; Lin, J.; Huang, P. In vivo three-dimensional multispectral photoacoustic imaging of dual enzyme-driven cyclic cascade reaction for tumor catalytic therapy. Nat. Commun. 2022, 13, 1298.
Wu, H. A.; Liu, L.; Song, L. N.; Ma, M.; Gu, N.; Zhang, Y. Enhanced tumor synergistic therapy by injectable magnetic hydrogel mediated generation of hyperthermia and highly toxic reactive oxygen species. ACS Nano 2019, 13, 14013–14023.