Incorporating Single-Copper Sites and Host Defense Peptides into aNanoreactor for Antibacterial Therapy by Bioinspired Design

Xuan Chen; Wei Luo; Qun Gao; Congrong Chen; Lichan Li; Dongbo Liu; Shaoyun Wang

doi:10.1016/j.eng.2024.09.021

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Engineering ›› 2024, Vol. 43 ›› Issue (12) : 216-227. DOI: 10.1016/j.eng.2024.09.021

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Incorporating Single-Copper Sites and Host Defense Peptides into aNanoreactor for Antibacterial Therapy by Bioinspired Design

Xuan Chen^a^,^b ,
Wei Luo^a ,
Qun Gao^a ,
Congrong Chen^a ,
Lichan Li^a ,
Dongbo Liu^b ,
Shaoyun Wang^a^,^*

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Abstract

A sustainable solution to the dramatic spread of antibiotic resistance threatening public health security is the development of antibiotic-free antimicrobial substances. Inspired by natural host defense mechanisms involving amino-terminal copper-nickel binding motif (ATCUN) antimicrobial peptides (AMPs), we have designed and prepared an artificial complex (Cu@G-AMPs) incorporating single-atom Cu catalysts for antibacterial therapy. The substrate of the complex, formed from guanine doped with abundant heteroatoms, anchored single Cu atoms with a coordination number of 2 and an average bond length of 1.91 Å. Interestingly, Cu@G-AMPs, exhibiting Fenton-like catalytic activity, caused the inactivation of methicillin-resistant Staphylococcus aureus (MRSA) by generating and delivering reactive oxygen species (ROS) cargo. Mechanistically, the intrinsic stress response system of MRSA underwent an irreversible collapse when Cu@G-AMPs initiated its offensive program associated with non-specific targets. Furthermore, Cu@G-AMPs, which inherited the immunomodulatory properties of AMPs, sequentially carried out the functions of pulling edge closure, stabilizing granulation tissue, promoting collagen fiber proliferation, alleviating inflammation, and promoting neovascularization in wound areas infected by MRSA. Our results show that Cu@G-AMPs will provide a new perspective on untangling the complex regulatory networks that resistant bacteria have cultivated to deactivate commercial antibiotics.

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Antimicrobial peptides / Single-atom catalysts / Fenton-like reactions / Antibacterial therapy

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Xuan Chen, Wei Luo, Qun Gao, Congrong Chen, Lichan Li, Dongbo Liu, Shaoyun Wang. Incorporating Single-Copper Sites and Host Defense Peptides into aNanoreactor for Antibacterial Therapy by Bioinspired Design. Engineering, 2024, 43(12): 216‒227 https://doi.org/10.1016/j.eng.2024.09.021

References

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[1]	Y. Wang, Q. Luo, T. Xiao, Y. Zhu, Y. Xiao. Impact of polymyxin resistance on virulence and fitness among clinically important gram-negative bacteria. Engineering, 13 (2022), pp. 178-185.

[2]	X. Chen, J. Han, X. Cai, S. Wang. Antimicrobial peptides: sustainable application informed by evolutionary constraints. Biotechnol Adv, 60 (2022), Article 108012.

[3]	A.W. Simonson, A.S. Mongia, M.R. Aronson, J.N. Alumasa, D.C. Chan, A. Lawanprasert, et al. Pathogen-specific antimicrobials engineered de novo through membrane-protein biomimicry. Nat Biomed Eng, 5 (5) (2021), pp. 467-480.

[4]	J.L. Narayana, B. Mishra, T. Lushnikova, Q. Wu, Y.S. Chhonker, Y. Zhang, et al. Two distinct amphipathic peptide antibiotics with systemic efficacy. Proc Natl Acad Sci USA, 117 (32) (2020), pp. 19446-19454.

[5]	C. Sun, W. Liu, L. Wang, R. Meng, J. Deng, R. Qing, et al. Photopolymerized keratin-PGLa hydrogels for antibiotic resistance reversal and enhancement of infectious wound healing. Mater Today Bio, 23 (2023), Article 100807.

[6]	Y. Wang, Y. Yang, Y. Shi, H. Song, C. Yu. Antibiotic-free antibacterial strategies enabled by nanomaterials: progress and perspectives. Adv Mater, 32 (18) (2020), Article 1904106.

[7]	H. Wang, M. Wang, X. Xu, P. Gao, Z. Xu, Q. Zhang, et al. Multi-target mode of action of silver against Staphylococcus aureus endows it with capability to combat antibiotic resistance. Nat Commun, 12 (1) (2021), pp. 3331-3413.

[8]	X. Yang, Q. Wei, H. Shao, X. Jiang. Multivalent aminosaccharide-based gold nanoparticles as narrow-spectrum antibiotics in vivo. ACS Appl Mater Interfaces, 11 (8) (2019), pp. 7725-7730.

[9]	Y. Qiao, J. He, W. Chen, Y. Yu, W. Li, Z. Du, et al. Light-activatable synergistic therapy of drug-resistant bacteria-infected cutaneous chronic wounds and nonhealing keratitis by cupriferous hollow nanoshells. ACS Nano, 14 (3) (2020), pp. 3299-3315.

[10]	A. Frei, A.D. Verderosa, A.G. Elliott, J. Zuegg, M.A.T. Blaskovich. Metals to combat antimicrobial resistance. Nat Rev Chem, 7 (3) (2023), pp. 202-224.

[11]	J. Portelinha, S.S. Duay, S.I. Yu, K. Heilemann, M.D.J. Libardo, S.A. Juliano, et al. Antimicrobial peptides and copper(II) ions: novel therapeutic opportunities. Chem Rev, 121 (4) (2021), pp. 2648-2712.

[12]	B.K. Maiti, N. Govil, T. Kundu, J.J.G. Moura. Designed metal-ATCUN derivatives: redox- and non-redox-based applications relevant for chemistry, biology, and medicine. iScience, 23 (12) (2020), Article 101792.

[13]	A.M. Pinkham, Z. Yu, J.A. Cowan. Attenuation of west nile virus NS2B/NS3 protease by amino terminal copper and nickel binding (ATCUN) peptides. J Med Chem, 61 (3) (2018), pp. 980-988.

[14]	C.M. Agbale, J.K. Sarfo, I.K. Galyuon, S.A. Juliano, G.G.O. Silva, D.F. Buccini, et al. Antimicrobial and antibiofilm activities of helical antimicrobial peptide sequences incorporating metal-binding motifs. Biochemistry, 58 (36) (2019), pp. 3802-3812.

[15]	Y. Zhou, S. Fan, L. Feng, X. Huang, X. Chen. Manipulating intratumoral fenton chemistry for enhanced chemodynamic and chemodynamic-synergized multimodal therapy. Adv Mater, 33 (48) (2021), Article 2104223.

[16]	B. Huang, Y. Liu, X. Huang, Z. Xie. Multiple heteroatom-doped few-layer carbons for the electrochemical oxygen reduction reaction. J Mater Chem A, 6 (44) (2018), pp. 22277-22286.

[17]	L. Shi, L. Wang, J. Chen, J. Chen, L. Ren, X. Shi, et al. Modifying graphene oxide with short peptide via click chemistry for biomedical applications. Appl Mater Today, 5 (2016), pp. 111-117.

[18]	X. Xie, T. Sun, J. Xue, Z. Miao, X. Yan, W. Fang, et al. Ag nanoparticles cluster with pH-triggered reassembly in targeting antimicrobial applications. Adv Funct Mater, 30 (17) (2020), Article 2000511.

[19]	M. Song, Y. Liu, X. Huang, S. Ding, Y. Wang, J. Shen, et al. A broad-spectrum antibiotic adjuvant reverses multidrug-resistant gram-negative pathogens. Nat Microbiol, 5 (8) (2020), pp. 1040-1050.

[20]	H.V. Ho, G. Tripathi, J. Gwon, S.Y. Lee, B.T. Lee. Novel TOCNF reinforced injectable alginate/β-tricalcium phosphate microspheres for bone regeneration. Mater Des, 194 (2020), Article 108892.

[21]	K. Fang, Y. Shen, K.H.R. Yie, Z. Zhou, L. Cai, S. Wu, et al. Preparation of zirconium hydrogen phosphate coatings on sandblasted/acid-etched titanium for enhancing its osteoinductivity and friction/corrosion resistance. IJN, 16 (2021), pp. 8265-8277.

[22]	Y. Yang, X. Wu, L. Ma, C. He, S. Cao, Y. Long, et al. Bioinspired spiky peroxidase-mimics for localized bacterial capture and synergistic catalytic sterilization. Adv Mater, 33 (8) (2021), Article 2005477.

[23]	X. Wang, C. Zhang, L. He, M. Li, P. Chen, W. Yang, et al. Near infrared II excitation nanoplatform for photothermal/chemodynamic/antibiotic synergistic therapy combating bacterial biofilm infections. J Nanobiotechnology, 21 (1) (2023), pp. 446-1413.

[24]	C. Xiao, L. Zhou, J. Gao, R. Jia, Y. Zheng, S. Zhao, et al. Musculus senhousei as a promising source of bioactive peptides protecting against alcohol-induced liver injury. Food Chem Toxicol, 174 (2023), Article 113652.

[25]	L. Tan, Z. Zhou, X. Liu, J. Li, Y. Zheng, Z. Cui, et al. Overcoming multidrug-resistant MRSA using conventional aminoglycoside antibiotics. Adv Sci, 7 (9) (2020), Article 1902070.

[26]	F. Bezrukov, J. Prados, A. Renzoni, O.O. Panasenko. MazF toxin causes alterations in Staphylococcus aureus transcriptome, translatome and proteome that underlie bacterial dormancy. Nucleic Acids Res, 49 (4) (2021), pp. 2085-2101.

[27]	B. Xu, H. Wang, W. Wang, L. Gao, S. Li, X. Pan, et al. A single-atom nanozyme for wound disinfection applications. Angew Chem Int Ed, 58 (15) (2019), pp. 4911-4916.

[28]	H. Chen, J. Cheng, X. Cai, J. Han, X. Chen, L. You, et al. pH-switchable antimicrobial supramolecular hydrogels for synergistically eliminating biofilm and promoting wound healing. ACS Appl Mater Interfaces, 14 (16) (2022), pp. 18120-18132.

[29]	W. Feng, G. Li, X. Kang, R. Wang, F. Liu, D. Zhao, et al. Cascade-targeting poly(amino acid) nanoparticles eliminate intracellular bacteria via on-site antibiotic delivery. Adv Mater, 34 (12) (2022), Article 2109789.

[30]	X. Arqué, M.D.T. Torres, T. Patiño, A. Boaro, S. Sánchez, C. de la Fuente-Nunez. Autonomous treatment of bacterial infections in vivo using antimicrobial micro- and nanomotors. ACS Nano, 16 (5) (2022), pp. 7547-7558.

[31]	X. Chen, X. Wu, S. Wang. An optimized antimicrobial peptide analog acts as an antibiotic adjuvant to reverse methicillin-resistant Staphylococcus aureus. NPJ Sci Food, 6 (1) (2022), p. 57.

[32]	Y. Wang, J. Mao, X. Meng, L. Yu, D. Deng, X. Bao. Catalysis with two-dimensional materials confining single atoms: concept, design, and applications. Chem Rev, 119 (3) (2019), pp. 1806-1854.

[33]	B. Wang, C. Cheng, M. Jin, J. He, H. Zhang, W. Ren, et al. A site distance effect induced by reactant molecule matchup in single-atom catalysts for Fenton-like reactions. Angew Chem Int Ed, 61 (33) (2022), Article e202207268.

[34]	H. Zhuo, X. Zhang, J. Liang, Q. Yu, H. Xiao, J. Li. Theoretical understandings of graphene-based metal single-atom catalysts: stability and catalytic performance. Chem Rev, 120 (21) (2020), pp. 12315-12341.

[35]	H. Fei, J. Dong, C. Wan, Z. Zhao, X. Xu, Z. Lin, et al. Microwave-assisted rapid synthesis of graphene-supported single atomic metals. Adv Mater, 30 (35) (2018), Article 1802146.

[36]	Z. Liu, H. Li, X. Gao, X. Guo, S. Wang, Y. Fang, et al. Rational highly dispersed ruthenium for reductive catalytic fractionation of lignocellulose. Nat Commun, 13 (1) (2022), p. 4716.

[37]	X. Zhang, X. Lin, X. Huang, Y. Chen, S. Lin, X. Huang, et al. Identification of role of nitrogen dopants in nanocarbon catalysis. Carbon Future, 1 (2) (2024), Article 9200008.

[38]	B. Lu, G. Zhu, C. Yu, G. Chen, C. Zhang, X. Zeng, et al. Functionalized graphene oxide nanosheets with unique three-in-one properties for efficient and tunable antibacterial applications. Nano Res, 14 (1) (2021), pp. 185-190.

[39]	Y. Di, Q. Lin, C. Chen, R.C. Montelaro, Y. Doi, B. Deslouches. Enhanced therapeutic index of an antimicrobial peptide in mice by increasing safety and activity against multidrug-resistant bacteria. Sci Adv, 6 (18) (2020), Article eaay6817.

[40]	M. Azizi-Lalabadi, H. Hashemi, J. Feng, S.M. Jafari. Carbon nanomaterials against pathogens; the antimicrobial activity of carbon nanotubes, graphene/graphene oxide, fullerenes, and their nanocomposites. Adv Colloid Interface Sci, 284 (2020), Article 102250.

[41]	X. Jin, F. Gao, M. Qin, Y. Yu, Y. Zhao, T. Shao, et al. How to make personal protective equipment spontaneously and continuously antimicrobial (incorporating oxidase-like catalysts). ACS Nano, 16 (5) (2022), pp. 7755-7771.

[42]	X. Wang, Q. Shi, Z. Zha, D. Zhu, L. Zheng, L. Shi, et al. Copper single-atom catalysts with photothermal performance and enhanced nanozyme activity for bacteria-infected wound therapy. Bioact Mater, 6 (12) (2021), pp. 4389-4401.

[43]	W. Xu, B. Sun, F. Wu, M. Mohammadniaei, Q. Song, X. Han, et al. Manganese single-atom catalysts for catalytic-photothermal synergistic anti-infected therapy. Chem Eng J, 438 (2022), Article 135636.

[44]	P. Tan, C. Wu, Q. Tang, T. Wang, C. Zhou, Y. Ding, et al. pH-triggered size-transformable and bioactivity-switchable self-assembling chimeric peptide nanoassemblies for combating drug-resistant bacteria and biofilms. Adv Mater, 35 (29) (2023), Article 2210766.

[45]	X. Lu, S. Gao, H. Lin, L. Yu, Y. Han, P. Zhu, et al. Bioinspired copper single-atom catalysts for tumor parallel catalytic therapy. Adv Mater, 32 (36) (2020), Article 2002246.

[46]

Song

, M.

, L.

Zhang

, X.

Zhang

, G.

Song

, M.

Huang

, et al. The protective effects of tripeptides VPP and IPP against small extracellular vesicles from angiotensin II-induced vascular smooth muscle cells mediating endothelial dysfunction in human umbilical vein endothelial cells. J Agric Food Chem, 68 (47) (2020), pp. 13730-13741.

[47]	J. Cheng, X. Lv, Y. Pan, D. Sun. Foodborne bacterial stress responses to exogenous reactive oxygen species (ROS) induced by cold plasma treatments. Trends Food Sci Technol, 103 (2020), pp. 239-247.

[48]	S. Mascharak, H.E. Talbott, M. Januszyk, M. Griffin, K. Chen, M.F. Davitt, et al. Multi-omic analysis reveals divergent molecular events in scarring and regenerative wound healing. Cell Stem Cell, 29 (2) (2022), pp. 315-327.e6.

[49]	S. Xu, A.D. Chisholm. C. elegans epidermal wounding induces a mitochondrial ROS burst that promotes wound repair. Dev Cell, 31 (1) (2014), pp. 48-60.

[50]	M.A. Fernandez-Yague, L.A. Hymel, C.E. Olingy, C. McClain, M.E. Ogle, J.R. García, et al. Analyzing immune response to engineered hydrogels by hierarchical clustering of inflammatory cell subsets. Sci Adv, 8 (8) (2022), Article eabd8056.

[51]	X. Xie, R. Wang, X. Zhang, Y. Ren, T. Du, Y. Ni, et al. A photothermal and self-induced Fenton dual-modal antibacterial platform for synergistic enhanced bacterial elimination. Appl Catal B, 295 (2021), Article 120315.