journal article·2020-12Open access

Amphiphilic silver nanoclusters show active nano–bio interaction with compelling antibacterial activity against multidrug-resistant bacteria

Yongjiu Chen, Liting Ren, Lingxiao Sun, Xuan Bai, Guoqiang Zhuang, Bin Cao, Guoqing Hu, Nanfeng Zheng, Sijin Liu

NPG Asia Materials· Volume 12· Issue 1

Abstract

Abstract Multidrug resistance represents a growing threat to human beings, and alternative antimicrobial regimens to conventional antibiotic paradigms are being extensively searched to fight against multidrug-resistant bacteria (MDRB). Although the antimicrobial potency of silver nanomaterials (AgNMs) has been previously elaborated, their efficacy against MDRB still remains to be strengthened. Here, our data revealed that small-sized silver nanoclusters (AgNCs) are superior to conventional silver nanoparticles (AgNPs) as robust antimicrobials against multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa). The core structure and surface ligands of AgNCs are crucial for the outstanding antibacterial activity of AgNCs. On the one hand, due to the presence of amphiphilic ligands, AgNCs are relatively prone to associate with the cell membrane and partake in endocytosis with targeted bacterial cells. Molecular dynamics simulations also corroborated this finding. On the other hand, the nanocluster structure of AgNCs led to strong peroxidase-like activity associated with massive production of reactive oxygen species (ROS), which contributes to their overall bactericidal potency. These outstanding features of AgNCs result in elevated bacterial killing efficacy by impairing the cell wall/membrane, promoting oxidative stress and attenuating pivotal cellular processes, e.g., ATP synthesis. Notably, AgNCs manifested great efficacy in treating P. aeruginosa-generated pneumonia in mice and increased the survival of infected animals, as well as exhibited excellent biocompatibility. Taken together, the results of this study pinpoint the great promise of AgNCs as new alternative therapeutics against MDR P. aeruginosa.
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Research context

OpenAlex topics: Nanocluster Synthesis and Applications · Advanced Nanomaterials in Catalysis · Nanoparticles: synthesis and applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (66)

Show source-provided references
1. Willyard, C. The drug-resistant bacteria that pose the greatest health threats. Nature 543, 15 (2017).10.1038/nature.2017.21550 ↗
2. Magiorakos, A.-P. et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect. 18, 268–281 (2012).10.1111/j.1469-0691.2011.03570.x ↗
3. Potron, A., Poirel, L. & Nordmann, P. Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: mechanisms and epidemiology. Int. J. Antimicrob. Ag. 45, 568–585 (2015).10.1016/j.ijantimicag.2015.03.001 ↗
4. Le Ouay, B. & Stellacci, F. Antibacterial activity of silver nanoparticles: a surface science insight. Nano Today 10, 339–354 (2015).10.1016/j.nantod.2015.04.002 ↗
5. Cui, Y. et al. The molecular mechanism of action of bactericidal gold nanoparticles on Escherichia coli. Biomaterials 33, 2327–2333 (2012).10.1016/j.biomaterials.2011.11.057 ↗
6. Lin, A. et al. Bacteria-responsive biomimetic selenium nanosystem for multidrug-resistant bacterial infection detection and inhibition. ACS Nano 13, 13965–13984 (2019).10.1021/acsnano.9b05766 ↗
7. Huang, N., Chen, X., Zhu, X., Xu, M. & Liu, J. Ruthenium complexes/polypeptide self-assembled nanoparticles for identification of bacterial infection and targeted antibacterial research. Biomaterials 141, 296–313 (2017).10.1016/j.biomaterials.2017.07.005 ↗
8. Jesline, A., John, N. P., Narayanan, P., Vani, C. & Murugan, S. Antimicrobial activity of zinc and titanium dioxide nanoparticles against biofilm-producing methicillin-resistant Staphylococcus aureus. Appl. Nanosci. 5, 157–162 (2015).10.1007/s13204-014-0301-x ↗
9. Masadeh, M. M. et al. Cerium oxide and iron oxide nanoparticles abolish the antibacterial activity of ciprofloxacin against gram positive and gram negative biofilm bacteria. Cytotechnology 67, 427–435 (2015).10.1007/s10616-014-9701-8 ↗
10. Zheng, H. et al. Engineered graphene oxide nanocomposite capable of preventing the evolution of antimicrobial resistance. ACS Nano 13, 11488–11499 (2019).10.1021/acsnano.9b04970 ↗
11. Chen, J. et al. Graphene oxide exhibits broad-spectrum antimicrobial activity against bacterial phytopathogens and fungal conidia by intertwining and membrane perturbation. Nanoscale 6, 1879–1889 (2014).10.1039/C3NR04941H ↗
12. Vranic, S. et al. Live imaging of label-free graphene oxide reveals critical factors causing oxidative-stress-mediated cellular responses. ACS Nano 12, 1373–1389 (2017).10.1021/acsnano.7b07734 ↗
13. Das, B. et al. Green synthesized silver nanoparticles destroy multidrug resistant bacteria via reactive oxygen species mediated membrane damage. Arab. J. Chem. 10, 862–876 (2017).10.1016/j.arabjc.2015.08.008 ↗
14. Cai, S. et al. Porous Pt/Ag nanoparticles with excellent multifunctional enzyme mimic activities and antibacterial effects. Nano Res. 10, 2056–2069 (2017).10.1007/s12274-016-1395-0 ↗
15. Wang, L.-S., Gupta, A. & Rotello, V. M. Nanomaterials for the treatment of bacterial biofilms. ACS Infect. Dis. 2, 3–4 (2016).10.1021/acsinfecdis.5b00116 ↗
16. Li, X. et al. Functional gold nanoparticles as potent antimicrobial agents against multi-drug-resistant bacteria. ACS Nano 8, 10682–10686 (2014).10.1021/nn5042625 ↗
17. Courtney, C. M. et al. Photoexcited quantum dots for killing multidrug-resistant bacteria. Nat. Mater. 15, 529–534 (2016).10.1038/nmat4542 ↗
18. Singh, R., Smitha, M. S. & Singh, S. P. The role of nanotechnology in combating multi-drug resistant bacteria. J. Nanosci. Nanotechnol. 14, 4745–4756 (2014).10.1166/jnn.2014.9527 ↗
19. O’Connell, K. M. G. et al. Combating multidrug-resistant bacteria: current strategies for the discovery of novel antibacterials. Angew. Chem. Int. Ed. 52, 10706–10733 (2013).10.1002/anie.201209979 ↗
20. Rai, M. K., Deshmukh, S. D., Ingle, A. P. & Gade, A. K. Silver nanoparticles: the powerful nanoweapon against multidrug-resistant bacteria. J. Appl. Microbiol. 112, 841–852 (2012).10.1111/j.1365-2672.2012.05253.x ↗
21. Franci, G. et al. Silver nanoparticles as potential antibacterial agents. Molecules 20, 8856–8874 (2015).10.3390/molecules20058856 ↗
22. Agnihotri, S., Mukherji, S. & Mukherji, S. Size-controlled silver nanoparticles synthesized over the range 5-100 nm using the same protocol and their antibacterial efficacy. RSC Adv. 4, 3974–3983 (2014).10.1039/C3RA44507K ↗
23. Sotiriou, G. A. & Pratsinis, S. E. Antibacterial activity of nanosilver ions and particles. Environ. Sci. Technol. 44, 5649–5654 (2010).10.1021/es101072s ↗
24. Chernousova, S. & Epple, M. Silver as antibacterial agent: ion, nanoparticle, and metal. Angew. Chem. Int. Ed. 52, 1636–1653 (2013).10.1002/anie.201205923 ↗
25. Panáček, A. et al. Silver colloid nanoparticles: synthesis, characterization, and their antibacterial activity. J. Phys. Chem. B 110, 16248–16253 (2006).10.1021/jp063826h ↗
26. Chaloupka, K., Malam, Y. & Seifalian, A. M. Nanosilver as a new generation of nanoproduct in biomedical applications. Trends Biotechnol. 28, 580–588 (2010).10.1016/j.tibtech.2010.07.006 ↗
27. Valden, M., Lai, X. & Goodman, D. W. Onset of catalytic activity of gold clusters on titania with the appearance of nonmetallic properties. Science 281, 1647–1650 (1998).10.1126/science.281.5383.1647 ↗
28. Suber, L. et al. Nanocluster superstructures or nanoparticles? The self-consuming scaffold decides. Nanoscale 10, 7472–7483 (2018).10.1039/C7NR09520A ↗
29. Yau, S. H., Varnavski, O. & Goodson, T. An ultrafast look at Au nanoclusters. Acc. Chem. Res 46, 1506–1516 (2013).10.1021/ar300280w ↗
30. Turner, M. et al. Selective oxidation with dioxygen by gold nanoparticle catalysts derived from 55-atom clusters. Nature 454, 981–983 (2008).10.1038/nature07194 ↗
31. Tian, X., Kong, X.-J., Zhu, Z.-M., Chen, T.-T. & Chu, X. A new label-free and turn-on strategy for endonuclease detection using a DNA–silver nanocluster probe. Talanta 131, 116–120 (2015).10.1016/j.talanta.2014.07.092 ↗
32. Yao, C. H. et al. Adding two active silver atoms on Au-25 nanoparticle. Nano Lett. 15, 1281–1287 (2015).10.1021/nl504477t ↗
33. Ren, L. T. et al. Bulky surface ligands promote surface reactivities of [Ag141X12(S-Adm)(40)](3+) (X=Cl, Br, I) nanoclusters: models for multiple-twinned nanoparticles. J. Am. Chem. Soc. 139, 13288–13291 (2017).10.1021/jacs.7b07926 ↗
34. Sun, Z. et al. Silver nanoclusters with specific ion recognition modulated by ligand passivation toward fluorimetric and colorimetric copper analysis and biological imaging. Sci. Rep. 6, 20553 (2016).
35. Cathcart, N. & Kitaev, V. Silver nanoclusters: single-stage scaleable synthesis of monodisperse species and their chirooptical properties. J. Phys. Chem. C. 114, 16010–16017 (2010).10.1021/jp101764q ↗
36. Diez, I. & Ras, R. H. A. Fluorescent silver nanoclusters. Nanoscale 3, 1963–1970 (2011).10.1039/c1nr00006c ↗
37. Dhanya, S., Saumya, V. & Rao, T. P. Synthesis of silver nanoclusters, characterization and application to trace level sensing of nitrate in aqueous media. Electrochim. Acta 102, 299–305 (2013).10.1016/j.electacta.2013.04.017 ↗
38. Feng, L. P. et al. Silver nanoclusters with enhanced fluorescence and specific ion recognition capability triggered by alcohol solvents: a highly selective fluorimetric strategy for detecting iodide ions in urine. Chem. Commun. 53, 9466–9469 (2017).10.1039/C7CC04924B ↗
39. Oh, E. et al. Meta-analysis of cellular toxicity for cadmium-containing quantum dots. Nat. Nanotechnol. 11, 479 (2016).10.1038/nnano.2015.338 ↗
40. Breiman, L. Random forests. Mach. Learn. 45, 5–32 (2001).10.1023/A:1010933404324 ↗
41. Yao, B. et al. Clinical and molecular characteristics of multi-clone carbapenem-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae isolates in a tertiary hospital in Beijing, China. Int. J. Infect. Dis. 37, 107–112 (2015).10.1016/j.ijid.2015.06.023 ↗
42. Wiegand, I., Hilpert, K. & Hancock, R. E. W. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat. Protoc. 3, 163 (2008).10.1038/nprot.2007.521 ↗
43. Zhang, Y. W. et al. Emergence of a hypervirulent carbapenem-resistant Klebsiella pneumoniae isolate from clinical infections in China. J. Infect. 71, 553–560 (2015).10.1016/j.jinf.2015.07.010 ↗
44. Zheng, K. Y., Setyawati, M. I., Lim, T. P., Leong, D. T. & Xie, J. P. Antimicrobial cluster bombs: silver nanoclusters packed with daptomycin. ACS Nano 10, 7934–7942 (2016).10.1021/acsnano.6b03862 ↗
45. Gutteridge, J. M. C. & Halliwell, B. The measurement and mechanism of lipid-peroxidation in biological-systems. Trends Biochem. Sci. 15, 129–135 (1990).10.1016/0968-0004(90)90206-Q ↗
46. Zhang, J., Wang, S. H., Gao, M., Li, R. B. & Liu, S. J. Multihierarchically profiling the biological effects of various metal-based nanoparticles in macrophages under low exposure doses. ACS Sustain. Chem. Eng. 6, 10374–10384 (2018).10.1021/acssuschemeng.8b01744 ↗
47. Wang, Z., Xia, T. & Liu, S. J. Mechanisms of nanosilver-induced toxicological effects: more attention should be paid to its sublethal effects. Nanoscale 7, 7470–7481 (2015).10.1039/C5NR01133G ↗
48. Qian, Y. et al. Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status. Biomaterials 70, 12–22 (2015).10.1016/j.biomaterials.2015.08.015 ↗
49. Chen, Y. et al. Nanosilver incurs an adaptive shunt of energy metabolism mode to glycolysis in tumor and nontumor cells. ACS Nano 8, 5813–5825 (2014).10.1021/nn500719m ↗
50. Marrink, S. J., Risselada, H. J., Yefimov, S., Tieleman, D. P. & de Vries, A. H. The MARTINI force field: coarse grained model for biomolecular simulations. J. Phys. Chem. B 111, 7812–7824 (2007).10.1021/jp071097f ↗
51. Baltoumas, F. A., Hamodrakas, S. J. & Iconomidou, V. A. The gram-negative outer membrane modeler: automated building of lipopolysaccharide-rich bacterial outer membranes in four force fields. J. Comput. Chem. 40, 1727–1734 (2019).10.1002/jcc.25823 ↗
52. Ma, H., Irudayanathan, F. J., Jiang, W. & Nangia, S. Simulating Gram-negative bacterial outer membrane: a coarse grain model. J. Phys. Chem. B 119, 14668–14682 (2015).10.1021/acs.jpcb.5b07122 ↗
53. Chiu, S. W., Scott, H. L. & Jakobsson, E. A coarse-grained model based on morse potential for water and n-alkanes. J. Chem. Theory Comput. 6, 851–863 (2010).10.1021/ct900475p ↗
54. Bai, X., Xu, L., Tang, J. Y., Zuo, Y. Y. & Hu, G. Adsorption of phospholipids at the air-water surface. Biophys. J. 117, 1224–1233 (2019).10.1016/j.bpj.2019.08.022 ↗
55. Hess, B., Kutzner, C., van der Spoel, D. & Lindahl, E. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4, 435–447 (2008).10.1021/ct700301q ↗
56. Spilker, T., Coenye, T., Vandamme, P. & LiPuma, J. J. PCR-based assay for differentiation of Pseudomonas aeruginosa from other Pseudomonas species recovered from cystic fibrosis patients. J. Clin. Microbiol. 42, 2074–2079 (2004).10.1128/JCM.42.5.2074-2079.2004 ↗
57. Wang, Y. Y., Wang, F. B., Wang, H. L. & Song, M. Y. Graphene oxide enhances the specificity of the polymerase chain reaction by modifying primer-template matching. Sci. Rep. 7, ARTN 16510 (2017).10.1038/s41598-017-16836-x ↗
58. Kumar Trivedi, M. Fourier transform infrared and ultraviolet-visible spectroscopic characterization of ammonium acetate and ammonium chloride: an impact of biofield treatment. Mod. Chem. Appl. 03, https://doi.org/10.4172/2329-6798.1000163 (2015).10.4172/2329-6798.1000163 ↗
59. Takele, H., Greve, H., Pochstein, C., Zaporojtchenko, V. & Faupel, F. Plasmonic properties of Ag nanoclusters in various polymer matrices. Nanotechnology 17, 3499–3505 (2006).10.1088/0957-4484/17/14/023 ↗
60. Gellatly, S. L. & Hancock, R. E. W. Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. Pathog. Dis. 67, 159–173 (2013).10.1111/2049-632X.12033 ↗
61. Fujitani, S., Sun, H. Y., Yu, V. L. & Weingarten, J. A. Pneumonia due to Pseudomonas aeruginosa part I: epidemiology, clinical diagnosis, and source. Chest 139, 909–919 (2011).10.1378/chest.10-0166 ↗
62. Aloush, V., Navon-Venezia, S., Seigman-Igra, Y., Cabili, S. & Carmeli, Y. Multidrug-resistant Pseudomonas aeruginosa: risk factors and clinical impact. Antimicrob. Agents Chemother. 50, 43–48 (2006).10.1128/AAC.50.1.43-48.2006 ↗
63. Gao, M. et al. Two‐dimensional Tin selenide (SnSe) nanosheets capable of mimicking key dehydrogenases in cellular metabolism. Angew. Chem. 132, 3647–3652 (2020).10.1002/ange.201913035 ↗
64. Chong, Y. et al. Palladium concave nanocrystals with high-index facets accelerate ascorbate oxidation in cancer treatment. Nat. Commun. 9, 1–10 (2018).10.1038/s41467-018-07257-z ↗
65. Xiu, Z. M., Zhang, Q. B., Puppala, H. L., Colvin, V. L. & Alvarez, P. J. J. Negligible particle-specific antibacterial activity of silver nanoparticles. Nano Lett. 12, 4271–4275 (2012).10.1021/nl301934w ↗
66. Kedziora, A. et al. Similarities and differences between silver ions and silver in nanoforms as antibacterial agents. Int. J. Mol. Sci. 19, ARTN 444 (2018).10.3390/ijms19020444 ↗