A self-assembled amino acid-based hydrogel with broad-spectrum antibacterial activity

Journal of Materials Science volume 56, pages7626–7636(2021)Cite this article

Abstract

Amino acid-based hydrogels with broad-spectrum antibacterial properties are increasingly popular alternatives to existing treatments in the fight against bacterial infection. Here, an amino acid-based hydrogel formed by the self-assembly of N-(9-fluorenylmethoxycarbonyl)-L-Leucine (Fmoc-L) and Fmoc-L-Lysine (Fmoc-K) is reported. The Fmoc-L/Fmoc-K hydrogel, which consisted of twisted nanobelts, displayed antibacterial activity against Gram-positive S. aureus, B. subtilis, L. monocytogenes, and Gram-negative E. coli, Sh. sonnei. Specifically, inhibition rates of 97%, 100%, 44%, 45%, and 32% were achieved against S. aureus, B. subtilis, L. monocytogenes, E. coli, and Sh. sonnei after incubation with 4 mM of an Fmoc-L/Fmoc-K hydrogel with the molar ratio of 3:1 for 2 h, respectively. The inhibition rates against E. coli and Sh. sonnei reached 80% and 55% after treatment with 10 mM hydrogel, respectively. The antibacterial activity of hydrogels was time-dependent and enhanced with the prolongation of time. Additionally, the antibacterial activity was easily tailored by modifying the molar ratio of Fmoc-L and Fmoc-K. It was found that Fmoc-L/Fmoc-K hydrogel targeted and destroyed the bacterial cell membrane, causing cytoplasmic leakage and eventually cell death. Moreover, the hydrogel also displayed antibacterial action by inducing the agglomeration of S. aureus. This work demonstrates the potential of amino acid-based hydrogels as a new class of effective antibacterial materials in biomedical applications.

Graphical abstract

A novel amino acid-based hydrogel formed by the self-assembly of Fmoc-L leucine and Fmoc-L lysine , which consisted of twisted nanobelts, displayed antibacterial activity against Gram-positive and Gram-negative bacteria.

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References

  1. 1

    Xie Y, Liu Y, Yang J, Liu Y, Hu F, Zhu K, Jiang X (2018) Gold nanoclusters for targeting methicillin-resistant staphylococcus aureus in vivo. Angew Chem Int Ed 57:3958–3962

    CAS  Article  Google Scholar 

  2. 2

    Siriwardena TN, Stach M, He R, Gan B-H, Javor S, Heitz M, Ma L, Cai X, Chen P, Wei D (2018) Lipidated peptide dendrimers killing multidrug-resistant bacteria. J Am Chem Soc 140:423–432

    CAS  Article  Google Scholar 

  3. 3

    Jamal M, Ahmad W, Andleeb S, Jalil F, Imran M, Nawaz MA, Hussain T, Ali M, Rafiq M, Kamil MA (2018) Bacterial biofilm and associated infections. J Chin Med Assoc 81:7–11

    Article  Google Scholar 

  4. 4

    Siah CJR, Childs C, Chia CK, Cheng KFK (2019) An observational study of temperature and thermal images of surgical wounds for detecting delayed wound healing within four days after surgery. J Clin Nurs 28:2285–2295

    Article  Google Scholar 

  5. 5

    Zhou J, Yao D, Qian Z, Hou S, Li L, Jenkins ATA, Fan Y (2018) Bacteria-responsive intelligent wound dressing: simultaneous In situ detection and inhibition of bacterial infection for accelerated wound healing. Biomaterials 161:11–23

    CAS  Article  Google Scholar 

  6. 6

    Zimmerli W (2014) Clinical presentation and treatment of orthopaedic implant-associated infection. J Int Med 276:111–119

    CAS  Article  Google Scholar 

  7. 7

    Kim T, Zhang Q, Li J, Zhang L, Jokerst JV (2018) A gold/silver hybrid nanoparticle for treatment and photoacoustic imaging of bacterial infection. ACS Nano 12:5615–5625

    CAS  Article  Google Scholar 

  8. 8

    Yang Y, Cai Z, Huang Z, Tang X, Zhang X (2018) Antimicrobial cationic polymers: from structural design to functional control. Polym J 50:33–44

    CAS  Article  Google Scholar 

  9. 9

    Bucekova M, Sojka M, Valachova I, Martinotti S, Ranzato E, Szep Z, Majtan V, Klaudiny J, Majtan J (2017) Bee-derived antibacterial peptide, defensin-1, promotes wound re-epithelialisation in vitro and in vivo. Sci Rep 7:1–13

    CAS  Article  Google Scholar 

  10. 10

    Koehbach J, Craik DJ (2019) The vast structural diversity of antimicrobial peptides. Trends Pharmacol Sci 40:517–528

    CAS  Article  Google Scholar 

  11. 11

    Lee MM, Xu W, Zheng L, Yu B, Leung AC, Kwok RT, Lam JW, Xu F-J, Wang D, Tang BZ (2020) Ultrafast discrimination of Gram-positive bacteria and highly efficient photodynamic antibacterial therapy using near-infrared photosensitizer with aggregation-induced emission characteristics. Biomaterials 230:119582

    CAS  Article  Google Scholar 

  12. 12

    Li X, Lee D, Huang J-D, Yoon J (2018) Phthalocyanine-assembled nanodots as photosensitizers for highly efficient type I photoreactions in photodynamic therapy. Angew Chemi Int Ed 57:9885–9890

    CAS  Article  Google Scholar 

  13. 13

    Malhotra K, Shankar S, Rai R, Singh Y (2018) Broad-spectrum antibacterial activity of proteolytically stable self-assembled αγ-hybrid peptide gels. Biomacromol 19:782–792

    CAS  Article  Google Scholar 

  14. 14

    Tian R, Qin X, Yuan P, Lei K, Wang L, Bai Y, Liu S, Chen X (2018) Fabrication of self-healing hydrogels with on-demand antimicrobial activity and sustained biomolecule release for infected skin regeneration. ACS Appl Mater Interfaces 10:17018–17027

    CAS  Article  Google Scholar 

  15. 15

    Li S, Dong S, Xu W, Tu S, Yan L, Zhao C, Ding J, Chen X (2018) Antibacterial hydrogels. Adv Sci 5:1700527

    Article  Google Scholar 

  16. 16

    Ramin MA, Latxague L, Sindhu KR, Chassande O, Barthélémy P (2017) Low molecular weight hydrogels derived from urea based-bolaamphiphiles as new injectable biomaterials. Biomaterials 145:72–80

    CAS  Article  Google Scholar 

  17. 17

    Nolan MC, Caparrós AMF, Dietrich B, Barrow M, Cross ER, Bleuel M, King SM, Adams DJ (2017) Optimising low molecular weight hydrogels for automated 3D printing. Soft Matter 13:8426–8432

    CAS  Article  Google Scholar 

  18. 18

    Xie Y, Huang R, Qi W, Wang Y, Su R, He Z (2016) Enzyme–substrate interactions promote the self-assembly of amino acid derivatives into supramolecular hydrogels. J Mater Chem B 4:844–851

    CAS  Article  Google Scholar 

  19. 19

    Chakraborty P, Gazit E (2018) Amino acid based self-assembled nanostructures: complex structures from remarkably simple building blocks. ChemNanoMat 4:730–740

    CAS  Article  Google Scholar 

  20. 20

    Tao K, Levin A, Adler-Abramovich L, Gazit E (2016) Fmoc-modified amino acids and short peptides: simple bio-inspired building blocks for the fabrication of functional materials. Chem Soc Rev 45:3935–3953

    CAS  Article  Google Scholar 

  21. 21

    Irwansyah I, Li YQ, Shi WX, Qi DP, Leow WR, Tang MBY, Li SZ, Chen XD (2015) Gram-positive antimicrobial activity of amino acid-based hydrogels. Adv Mater 27:648–654

    CAS  Article  Google Scholar 

  22. 22

    Gahane AY, Ranjan P, Singh V, Sharma RK, Sinha N, Sharma M, Chaudhry R, Thakur AK (2018) Fmoc-phenylalanine displays antibacterial activity against Gram-positive bacteria in gel and solution phases. Soft Matter 14:2234–2244

    CAS  Article  Google Scholar 

  23. 23

    Zhao Q, Zhao Y, Lu Z, Tang Y (2019) Amino acid-modified conjugated oligomer self-assembly hydrogel for efficient capture and specific killing of antibiotic-resistant bacteria. ACS Appl Mater Interfaces 11:16320–16327

    CAS  Article  Google Scholar 

  24. 24

    Song J, Yuan C, Jiao T, Xing R, Yang M, Adams DJ, Yan X (2020) Multifunctional antimicrobial biometallohydrogels based on amino acid coordinated self-assembly. Small 16:1907309

    CAS  Article  Google Scholar 

  25. 25

    Xie Y-Y, Zhang Y-W, Qin X-T, Liu L-P, Wahid F, Zhong C, Jia S-R (2020) Structure-dependent antibacterial activity of amino acid-based supramolecular hydrogels. Colloids Surf B Biointerfaces 193:111099

    CAS  Article  Google Scholar 

  26. 26

    Akter M, Sikder MT, Rahman MM, Ullah AA, Hossain KFB, Banik S, Hosokawa T, Saito T, Kurasaki M (2018) A systematic review on silver nanoparticles-induced cytotoxicity: physicochemical properties and perspectives. J Adv Res 9:1–16

    CAS  Article  Google Scholar 

  27. 27

    Dinarello CA (2010) Anti-inflammatory agents: present and future. Cell 140:935–950

    CAS  Article  Google Scholar 

  28. 28

    Ma Q, Lv Y, Gu Y, Dong N, Li D, Shan A (2013) Rational design of cationic antimicrobial peptides by the tandem of leucine-rich repeat. Amino Acids 44:1215–1224

    CAS  Article  Google Scholar 

  29. 29

    Yang ZM, Gu HW, Zhang Y, Wang L, Xu B (2004) Small molecule hydrogels based on a class of antiinflammatory agents. Chem Commun. https://doi.org/10.1039/b310574a

    Article  Google Scholar 

  30. 30

    Kumari S, Rajit Prasad S, Mandal D, Das P (2019) Carbon dot-DNA-protoporphyrin hybrid hydrogel for sustained photoinduced antimicrobial activity. J Colloid Interface Sci 553:228–238

    CAS  Article  Google Scholar 

  31. 31

    Villanueva ME, Cuestas ML, Perez CJ, Campo Dall Orto V, Copello GJ (2019) Smart release of antimicrobial ZnO nanoplates from a pH-responsive keratin hydrogel. J Colloid Interface Sci 536:372–380

    CAS  Article  Google Scholar 

  32. 32

    Liang Y, Zhao X, Ma PX, Guo B, Du Y, Han X (2019) pH-responsive injectable hydrogels with mucosal adhesiveness based on chitosan-grafted-dihydrocaffeic acid and oxidized pullulan for localized drug delivery. J Colloid Interface Sci 536:224–234

    CAS  Article  Google Scholar 

  33. 33

    Huang X, Wang P, Li T, Tian X, Guo W, Xu B, Huang G, Cai D, Zhou F, Zhang H, Lei H (2020) Self-assemblies based on traditional medicine berberine and cinnamic acid for adhesion-induced inhibition multidrug-resistant staphylococcus aureus. ACS Appl Mater Interfaces 12:227–237

    CAS  Article  Google Scholar 

  34. 34

    Amdursky N, Stevens MM (2015) Circular dichroism of amino acids: following the structural formation of phenylalanine. ChemPhysChem 16:2768–2774

    CAS  Article  Google Scholar 

  35. 35

    Xing Q, Zhang J, Xie Y, Wang Y, Qi W, Rao H, Su R, He Z (2018) Aromatic motifs dictate nanohelix handedness of tripeptides. ACS Nano 12:12305–12314

    CAS  Article  Google Scholar 

  36. 36

    Xie Y, Wang X, Huang R, Qi W, Wang Y, Su R, He Z (2015) Electrostatic and aromatic interaction-directed supramolecular self-assembly of a designed fmoc-tripeptide into helical nanoribbons. Langmuir 31:2885–2894

    CAS  Article  Google Scholar 

  37. 37

    Hu B, Shen Y, Adamcik J, Fischer P, Schneider M, Loessner MJ, Mezzenga R (2018) Polyphenol-binding amyloid fibrils self-assemble into reversible hydrogels with antibacterial activity. ACS Nano 12:3385–3396

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 21808169), Scientific Research Plan Project of Tianjin Municipal Education Commission (Nos. 2018KJ121), and the Natural Science Foundation of Tianjin (Grant 19PTSYJC00060).

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Affiliations

  1. State Key Laboratory of Food Nutrition andSafety, Tianjin University of Science and Technology, Tianjin, People’s Republic of China

    Yan-Yan Xie, Xiao-Tong Qin, Jia-Yuan Feng, Cheng Zhong & Shi-Ru Jia

  2. Key Laboratory of Industrial Fermentation Microbiology, (Ministry of Education), Tianjin University of Science and Technology, Tianjin, People’s Republic of China

    Yan-Yan Xie, Xiao-Tong Qin, Jia-Yuan Feng, Cheng Zhong & Shi-Ru Jia

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  1. Yan-Yan Xie
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  2. Xiao-Tong Qin
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  4. Cheng Zhong
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  5. Shi-Ru Jia
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Correspondence to Yan-Yan Xie or Cheng Zhong.

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Xie, YY., Qin, XT., Feng, JY. et al. A self-assembled amino acid-based hydrogel with broad-spectrum antibacterial activity. J Mater Sci 56, 7626–7636 (2021). https://doi.org/10.1007/s10853-021-05801-9

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