AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article

A peroxidase-like single-atom Fe-N5 active site for effective killing human lung adenocarcinoma cells

Liye Zhu1, Hong Zhong2, Dan Du2, Tao Li4,5, Hoai Nguyen6, Scott P. Beckman2, Wentao Xu1, Jin-Cheng Li3( ), Nan Cheng1( ), Yuehe Lin2( )
Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA
Faculty of Chemical Engineering, Yunnan Provincial Key Laboratory of Energy Saving in Phosphorus Chemical Engineering and New Phosphorus Materials, Kunming University of Science and Technology, Kunming 650500, China
Department of Chemistry and Biochemistry, Northern Illinois University, 1425 W. Lincoln Hwy., DeKalb, IL 60115, USA
X-ray Science Division, Argonne National Laboratory, 9700 S. Cass Ave, Lemont, IL 60439, USA
Material Science Division, Argonne National Laboratory, 9700 S. Cass Ave, Lemont, IL 60439, USA
Show Author Information

Graphical Abstract

We designed and synthesized an atomic Fe-N5 decorated graphene nanosheet (Fe-N5/GN SAC). Through enzymology and theoretical calculations, the Fe-N5/GN SAC possesses outstanding intrinsic peroxidase-like catalytic activity, and could be used as a single-atom catalyst to kill lung cancer cells in a three-dimensional (3D) cancer cell model.

Abstract

Single-atom catalyst (SAC) is one of the newest catalysts, and attracts people’s wide attention in cancer therapy based on their characteristics of maximum specific catalytic activity and high stability. We designed and synthesized a Fe-N decorated graphene nanosheet (Fe-N5/GN SAC) with the coordination number of five. Through enzymology and theoretical calculations, the Fe-N5/GN SAC has outstanding intrinsic peroxidase-like catalytic activity due to single-atom Fe site with five-N-coordination structure. We explored its potential on lung cancer therapy, and found that it could kill human lung adenocarcinoma cells (A549) by decomposing hydrogen peroxide (H2O2) into toxic reactive oxygen species (ROS) under acidic microenvironment in three-dimensional (3D) lung cancer cell model. Our study demonstrates a promising application of SAC with highly efficient single-atom catalytic sites for cancer treatment.

Keywords

single-atom catalystthree-dimensional (3D)cancer cell modelperoxidase-like catalytic activitycancer therapy

Electronic Supplementary Material

Download File(s)
12274_2022_5127_MOESM1_ESM.pdf (495.3 KB)

References

[1]

Thai, A. A.; Solomon, B. J.; Sequist, L. V.; Gainor, J. F.; Heist, R. S. Lung cancer. Lancet 2021, 398, 535–554.
Crossref Google Scholar
[2]

Li, S. S.; Shang, L.; Xu, B. L.; Wang, S. H.; Gu, K.; Wu, Q. Y.; Sun, Y.; Zhang, Q. H.; Yang, H. L.; Zhang, F. R. et al. A nanozyme with photo-enhanced dual enzyme-like activities for deep pancreatic cancer therapy. Angew. Chem., Int. Ed. 2019, 58, 12624–12631.
Crossref Google Scholar
[3]

Cheng, N.; Li, J. C.; Liu, D.; Lin, Y. H.; Du, D. Single-atom nanozyme based on nanoengineered Fe-N-C catalyst with superior peroxidase-like activity for ultrasensitive bioassays. Small 2019, 15, 1901485.
Crossref Google Scholar
[4]

Jiao, L.; Xu, W. Q.; Wu, Y.; Yan, H. Y.; Gu, W. L.; Du, D.; Lin, Y. H.; Zhu, C. Z. Single-atom catalysts boost signal amplification for biosensing. Chem. Soc. Rev. 2021, 50, 750–765.
Crossref Google Scholar
[5]

Wang, X. W.; Fan, L. X.; Cheng, L.; Sun, Y. B.; Wang, X. Y.; Zhong, X. Y.; Shi, Q. Q.; Gong, F.; Yang, Y.; Ma, Y. et al. Biodegradable nickel disulfide nanozymes with GSH-depleting function for high-efficiency photothermal-catalytic antibacterial therapy. iScience 2020, 23, 101281.
Crossref Google Scholar
[6]

Xu, B. L.; Wang, H.; Wang, W. W.; Gao, L. Z.; Li, S. S.; Pan, X. T.; Wang, H. Y.; Yang, H. L.; Meng, X. Q.; Wu, Q. W. et al. A single-atom nanozyme for wound disinfection applications. Angew. Chem., Int. Ed. 2019, 58, 4911–4916.
Crossref Google Scholar
[7]

Wang, D. D.; Wu, H. H.; Phua, S. Z. F.; Yang, G. B.; Lim, W. Q.; Gu, L.; Qian, C.; Wang, H. B.; Guo, Z.; Chen, H. Z. et al. Self-assembled single-atom nanozyme for enhanced photodynamic therapy treatment of tumor. Nat. Commun. 2020, 11, 357.
Crossref Google Scholar
[8]

Luo, Y. N.; Song, Y.; Wang, M. M.; Jian, T. Y.; Ding, S. C.; Mu, P.; Liao, Z. H.; Shi, Q. R.; Cai, X. L.; Jin, H. B. et al. Bioinspired peptoid nanotubes for targeted tumor cell imaging and chemo-photodynamic therapy. Small 2019, 15, e1902485.
Crossref Google Scholar
[9]

Zhou, X. T.; You, M.; Wang, F. H.; Wang, Z. Z.; Gao, X. F.; Jing, C.; Liu, J. M.; Guo, M. Y.; Li, J. Y.; Luo, A. P. et al. Multifunctional graphdiyne-cerium oxide nanozymes facilitate microRNA delivery and attenuate tumor hypoxia for highly efficient radiotherapy of esophageal cancer. Adv. Mater. 2021, 33, e2100556.
Crossref Google Scholar
[10]

Ning, S. P.; Zheng, Y.; Qiao, K.; Li, G. Z.; Bai, Q.; Xu, S. P. Laser-triggered combination therapy by iron sulfide-doxorubicin@functionalized nanozymes for breast cancer therapy. J. Nanobiotechnol. 2021, 19, 344.
Crossref Google Scholar
[11]

Cai, X. L.; Wang, M. M.; Mu, P.; Jian, T. Y.; Liu, D.; Ding, S. C.; Luo, Y. N.; Du, D.; Song, Y.; Chen, C. L. et al. Sequence-defined nanotubes assembled from IR780-conjugated peptoids for chemophototherapy of malignant glioma. Research 2021, 2021, 9861384.
Google Scholar
[12]

Shen, L. H.; Ye, D. X.; Zhao, H. B.; Zhang, J. J. Perspectives for single-atom nanozymes: Advanced synthesis, functional mechanisms, and biomedical applications. Anal. Chem. 2021, 93, 1221–1231.
Crossref Google Scholar
[13]

Zhao, C.; Xiong, C.; Liu, X. K.; Qiao, M.; Li, Z. J.; Yuan, T. W.; Wang, J.; Qu, Y. T.; Wang, X. Q.; Zhou, F. Y. et al. Unraveling the enzyme-like activity of heterogeneous single atom catalyst. Chem. Commun. 2019, 55, 2285–2288.
Crossref Google Scholar
[14]

Jiao, L.; Yan, H. Y.; Wu, Y.; Gu, W. L.; Zhu, C. Z.; Du, D.; Lin, Y. H. When nanozymes meet single-atom catalysis. Angew. Chem., Int. Ed. 2020, 59, 2565–2576.
Crossref Google Scholar
[15]

Xu, B.; Cui, Y.; Wang, W.; Li, S.; Lyu, C.; Wang, S.; Bao, W.; Wang, H.; Qin, M.; Liu, Z.; Wei, W.; Liu, H. Immunomodulation-enhanced nanozyme-based tumor catalytic therapy. Adv. Mater. 2020, 32, e2003563.
Crossref Google Scholar
[16]

Lyu, Z.; Ding, S.; Tieu, P.; Fang, L.; Li, X.; Li, T.; Pan, X.; Engelhard, M. H.; Ruan, X.; Du, D.; Li, S.; Lin, Y. Single-atomic site catalyst enhanced lateral flow immunoassay for point-of-care detection of herbicide. Research (Washington, D.C.). 2022, 2022, 9823290.
Google Scholar
[17]

Niu, X. H.; Shi, Q. R.; Zhu, W. L.; Liu, D.; Tian, H. Y.; Fu, S. F.; Cheng, N.; Li, S. Q.; Smith, J. N.; Du, D. et al. Unprecedented peroxidase-mimicking activity of single-atom nanozyme with atomically dispersed Fe-NX moieties hosted by MOF derived porous carbon. Biosens. Bioelectron. 2019, 142, 111495.
Crossref Google Scholar
[18]

Fu, S. F.; Zhu, C. Z.; Su, D.; Song, J. H.; Yao, S. Y.; Feng, S.; Engelhard, M. H.; Du, D.; Lin, Y. H. Porous carbon-hosted atomically dispersed iron-nitrogen moiety as enhanced electrocatalysts for oxygen reduction reaction in a wide range of pH. Small 2018, 14, 1703118.
Crossref Google Scholar
[19]
Koledova, Z. 3D cell culture: An introduction. In 3D Cell Culture. Koledova, Z. , Ed.; Springer: New York, 2017; pp 1–11.
[20]

Ravi, M.; Paramesh, V.; Kaviya, S. R.; Anuradha, E.; Solomon, F. D. P. 3D cell culture systems: Advantages and applications. J. Cell. Physiol. 2015, 230, 16–26.
Crossref Google Scholar
[21]

Zhu, C. Z.; Shi, Q. R.; Xu, B. Z.; Fu, S. F.; Wan, G.; Yang, C.; Yao, S. Y.; Song, J. H.; Zhou, H.; Du, D. et al. Hierarchically porous M-N-C (M = Co and Fe) single-atom electrocatalysts with robust MNX active moieties enable enhanced ORR performance. Adv. Energy Mater. 2018, 8, 1801956.
Crossref Google Scholar
[22]
Li, J. C.; Yang, Z. Q.; Tang, D. M.; Zhang, L. L.; Hou, P. X.; Zhao, S. Y.; Liu, C.; Cheng, M.; Li, G. X.; Zhang, F. et al. N-doped carbon nanotubes containing a high concentration of single iron atoms for efficient oxygen reduction. NPG Asia Mater. 2018, 10, e461.
[23]

Li, J. C.; Xiao, F.; Zhong, H.; Li, T.; Xu, M. J.; Ma, L.; Cheng, M.; Liu, D.; Feng, S.; Shi, Q. R. et al. Secondary-atom-assisted synthesis of single iron atoms anchored on N-doped carbon nanowires for oxygen reduction reaction. ACS Catal. 2019, 9, 5929–5934.
Crossref Google Scholar
[24]

Li, J. C.; Hou, P. X.; Zhao, S. Y.; Liu, C.; Tang, D. M.; Cheng, M.; Zhang, F.; Cheng, H. M. A 3D bi-functional porous N-doped carbon microtube sponge electrocatalyst for oxygen reduction and oxygen evolution reactions. Energy Environ. Sci. 2016, 9, 3079–3084.
Crossref Google Scholar
[25]

Li, J. C.; Meng, Y.; Zhang, L. L.; Li, G. Z.; Shi, Z. C.; Hou, P. X.; Liu, C.; Cheng, H. M.; Shao, M. H. Dual-phasic carbon with Co single atoms and nanoparticles as a bifunctional oxygen electrocatalyst for rechargeable Zn-air batteries. Adv. Funct. Mater. 2021, 31, 2103360.
Crossref Google Scholar
[26]

Liang, H. W.; Wei, W.; Wu, Z. S.; Feng, X. L.; Müllen, K. Mesoporous metal-nitrogen-doped carbon electrocatalysts for highly efficient oxygen reduction reaction. J. Am. Chem. Soc. 2013, 135, 16002–16005.
Crossref Google Scholar
[27]

Zhu, C. Z.; Fu, S. F.; Song, J. H.; Shi, Q. R.; Su, D.; Engelhard, M. H.; Li, X. L.; Xiao, D. D.; Li, D.; Estevez, L. et al. Self-assembled Fe-N-doped carbon nanotube aerogels with single-atom catalyst feature as high-efficiency oxygen reduction electrocatalysts. Small 2017, 13, 1603407.
Crossref Google Scholar
[28]

Huo, M. F.; Wang, L. Y.; Wang, Y. W.; Chen, Y.; Shi, J. L. Nanocatalytic tumor therapy by single-atom catalysts. ACS Nano 2019, 13, 2643–2653.
Google Scholar
[29]

Ahmed, Y.; Yaakob, Z.; Akhtar, P. Degradation and mineralization of methylene blue using a heterogeneous photo-Fenton catalyst under visible and solar light irradiation. Catal. Sci. Technol. 2016, 6, 1222–1232.
Crossref Google Scholar
[30]

Celardo, I.; Pedersen, J. Z.; Traversa, E.; Ghibelli, L. Pharmacological potential of cerium oxide nanoparticles. Nanoscale 2011, 3, 1411–1420.
Crossref Google Scholar
[31]

Herget, K.; Hubach, P.; Pusch, S.; Deglmann, P.; Götz, H.; Gorelik, T. E.; Gural'skiy, I. A.; Pfitzner, F.; Link, T.; Schenk, S. et al. Haloperoxidase mimicry by CeO2−X nanorods combats biofouling. Adv. Mater. 2017, 29, 1603823.
Crossref Google Scholar
[32]

Jiao, L.; Wu, J. B.; Zhong, H.; Zhang, Y.; Xu, W. Q.; Wu, Y.; Chen, Y. F.; Yan, H. Y.; Zhang, Q. H.; Gu, W. L. et al. Densely isolated FeN4 sites for peroxidase mimicking. ACS Catal. 2020, 10, 6422–6429.
Crossref Google Scholar
[33]

Hwang, J.; Rao, R. R.; Giordano, L.; Katayama, Y.; Yu, Y.; Shao-Horn, Y. Perovskites in catalysis and electrocatalysis. Science 2017, 358, 751–756.
Crossref Google Scholar
[34]

Xia, D. S.; Yang, X.; Xie, L.; Wei, Y. P.; Jiang, W.; Dou, M.; Li, X. N.; Li, J.; Gan, L.; Kang, F. Y. Direct growth of carbon nanotubes doped with single atomic Fe-N4 active sites and neighboring graphitic nitrogen for efficient and stable oxygen reduction electrocatalysis. Adv. Funct. Mater. 2019, 29, 1906174.
Crossref Google Scholar
[35]

Jing, X. M.; Yang, F. M.; Shao, C. C.; Wei, K.; Xie, M. Y.; Shen, H.; Shu, Y. Q. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol. Cancer. 2019, 18, 157.
Crossref Google Scholar
[36]

Sosa, V.; Moliné, T.; Somoza, R.; Paciucci, R.; Kondoh, H.; LLeonart, M. E. Oxidative stress and cancer: An overview. Ageing Res. Rev. 2013, 12, 376–390.
Crossref Google Scholar
[37]

Kovacic, P.; Jacintho, J. D. Mechanisms of carcinogenesis focus on oxidative stress and electron transfer. Curr. Med. Chem. 2001, 8, 773–796.
Crossref Google Scholar
[38]

Wu, Z. M.; Wang, H. G.; Fang, S. Y.; Xu, C. Y. Roles of endoplasmic reticulum stress and autophagy on H2O2-induced oxidative stress injury in HepG2 cells. Mol. Med. Rep. 2018, 18, 4163–4174.
Google Scholar
[39]

Cui, L.; Bu, W. Q.; Song, J.; Feng, L.; Xu, T. T.; Liu, D.; Ding, W. B.; Wang, J. H.; Li, C. Y.; Ma, B. G. et al. Apoptosis induction by alantolactone in breast cancer MDA-MB-231 cells through reactive oxygen species-mediated mitochondrion-dependent pathway. Arch. Pharm. Res. 2018, 41, 299–313.
Crossref Google Scholar
[40]

Kaminskyy, V. O.; Zhivotovsky, B. Free radicals in cross talk between autophagy and apoptosis. Antioxid. Redox Signal. 2014, 21, 86–102.
Crossref Google Scholar
[41]
Brentnall, M.; Rodriguez-Menocal, L.; De Guevara, R. L.; Cepero, E.; Boise, L. H. Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol. 2013, 14, 32.
[42]

Linder, M.; Tschernig, T. Vasculogenic mimicry: Possible role of effector caspase-3, caspase-6 and caspase-7. Ann. Anat. 2016, 204, 114–117.
Crossref Google Scholar
[43]

Rodríguez-González, J.; Wilkins-Rodríguez, A. A.; Gutiérrez-Kobeh, L. Role of glutathione, ROS, and Bcl-xL in the inhibition of apoptosis of monocyte-derived dendritic cells by Leishmania mexicana promastigotes. Parasitol. Res. 2018, 117, 1225–1235.
Crossref Google Scholar
[44]

Li, J.-C.; Zhong, H.; Xu, M.; Li, T.; Wang, L.; Shi, Q.; Feng, S.; Lyu, Z.; Liu, D.; Du, D.; Beckman, S. P.; Pan, X.; Lin, Y.; Shao, M. Boosting the activity of Fe-Nx moieties in Fe-N-C electrocatalysts via phosphorus doping for oxygen reduction reaction. Science China Materials. 2020, 63, 965–971.
Crossref Google Scholar
[45]

Jiang, B.; Duan, D. M.; Gao, L. Z.; Zhou, M. J.; Fan, K. L.; Tang, Y.; Xi, J. Q.; Bi, Y. H.; Tong, Z.; Gao, G. F. et al. Standardized assays for determining the catalytic activity and kinetics of peroxidase-like nanozymes. Nat. Protoc. 2018, 13, 1506–1520.
Crossref Google Scholar
[46]

Hohenberg, P.; Kohn, W. Inhomogeneous electron gas. Phys. Rev. 1964, 136, B864–B871.
Crossref Google Scholar
[47]

Kohn, W.; Sham, L. J. Self-consistent equations including exchange and correlation effects. Phys. Rev. 1965, 140, A1133–A1138.
Crossref Google Scholar
[48]

Perkinson, J. C.; Swenson, J. M.; DeMasi, A.; Wagenbach, C.; Ludwig, K. F.; Norris, S. A.; Aziz, M. J. Sawtooth structure formation under nonlinear-regime ion bombardment. J. Phys. Condens. Matter. 2018, 30, 294004.
Crossref Google Scholar
[49]

Kresse, G.; Joubert, D. From ultrasoft pseudopotentials to the projector augmented-wave method. Phys. Rev. B 1999, 59, 1758–1775.
Google Scholar
[50]

Perdew, J. P.; Burke, K.; Ernzerhof, M. Generalized gradient approximation made simple. Phys. Rev. Lett. 1996, 77, 3865–3868.
Crossref Google Scholar
[51]

Huang, L.; Chen, J. X.; Gan, L. F.; Wang, J.; Dong, S. J. Single-atom nanozymes. Sci. Adv. 2019, 5, eaav5490.
Crossref Google Scholar
[52]

Zhang, H. N.; Li, J.; Xi, S. B.; Du, Y. H.; Hai, X.; Wang, J. Y.; Xu, H. M.; Wu, G.; Zhang, J.; Lu, J. et al. A graphene-supported single-atom FeN5 catalytic site for efficient electrochemical CO2 reduction. Angew. Chem., Int. Ed. 2019, 58, 14871–14876.
Crossref Google Scholar
[53]

Monkhorst, H. J.; Pack, J. D. Special points for Brillouin-zone integrations. Phys. Rev. B 1976, 13, 5188–5192.
Crossref Google Scholar
[54]

Grimme, S. Semiempirical GGA-type density functional constructed with a long-range dispersion correction. J. Comput. Chem. 2006, 27, 1787–1799.
Crossref Google Scholar
[55]

Zhu, L. Y.; Wang, H. M.; Yuhan, J.; Zhang, B. Y.; Li, H. Y.; Asakiya, C.; Huang, K. L.; He, X. Y.; Xu, W. T. Exosomes mediated the delivery of ochratoxin A-induced cytotoxicity in HEK293 cells. Toxicology 2021, 461, 152926.
Crossref Google Scholar
Nano Research
Volume 16 Issue 4,
April 2023
Pages 5216-5225
DOI: 10.1007/s12274-022-5127-3
Cite this article:
Zhu L, Zhong H, Du D, et al. A peroxidase-like single-atom Fe-N5 active site for effective killing human lung adenocarcinoma cells. Nano Research, 2023, 16(4): 5216-5225. https://doi.org/10.1007/s12274-022-5127-3
Topics:
Nano biologySynthesis

6773

Views

12

Crossref

13

Web of Science

13

Scopus

0

CSCD

Altmetrics
Received: 11 August 2022
Revised: 28 September 2022
Accepted: 30 September 2022
Published: 23 November 2022
© Tsinghua University Press 2022
Return