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Synthesis of the ternary nanocomposites composed of zinc 2-methylimidazolate frameworks, lactoferrin and melittin for antifungal therapy

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Abstract

Fungal infections caused by Candida albicans and related pathogenic fungi are threatening the health of millions of people worldwide. Natural antimicrobial peptides are promising candidates for antimicrobial therapy, but their application is compromised by their toxicity to mammalian cells. In this study, zeolitic imidazolate framework-8 nanosheets (ZM), the fungus-targeting lactoferrin (LFP), and the model antimicrobial peptide melittin (Mel) were co-assembled to form ternary nanocomposites by electrostatic interaction for treating pathogenic fungal infections. The results showed that the ternary nanocomposites ZM+LFP+Mel exhibited strong inhibitory activity against growth of the fungal pathogen C. albicans and had stronger capacity to eradicate fungal biofilms than free Mel. The in vivo mice wound model further showed that the nanocomposites had excellent anti-infection ability and drastically promoted wound healing. This study provides a facile strategy to detoxify antimicrobial peptides and to enhance its antimicrobial efficiency for biomedical application.

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References

  1. Schwartz RA (2004) Superficial fungal infections. Lancet 364:1173–1182. https://doi.org/10.1016/s0140-6736(04)17107-9

    Article  Google Scholar 

  2. Rautemaa-Richardson R, Richardson MD (2017) Systemic fungal infections. Medicine 45:757–762. https://doi.org/10.1016/j.mpmed.2013.09.011

    Article  Google Scholar 

  3. Mani Chandrika KVS, Sharma S (2020) Promising antifungal agents: a mini review. Bioorgan Med Chem 28:115398. https://doi.org/10.1016/j.bmc.2020.115398

    Article  CAS  Google Scholar 

  4. Howard KC, Dennis EK, Watt DS, Garneau-Tsodikova S (2020) A comprehensive overview of the medicinal chemistry of antifungal drugs: perspectives and promise. Chem Soc Rev 49:2426–2480. https://doi.org/10.1039/c9cs00556k

    Article  CAS  Google Scholar 

  5. Campoy S, Adrio JL (2017) Antifungals. Biochem Pharmacol 133:86–96. https://doi.org/10.1016/j.bcp.2016.11.019

    Article  CAS  Google Scholar 

  6. Stewart AG, Paterson DL (2021) How urgent is the need for new antifungals? Expert Opin Pharmaco 22:1857–1870. https://doi.org/10.1080/14656566.2021.1935868

    Article  Google Scholar 

  7. Lazzaro BP, Zasloff M, Rolff J (2020) Antimicrobial peptides application informed by evolution. Science 368:eaau5480. https://doi.org/10.1126/science.aau5480

    Article  CAS  Google Scholar 

  8. Gan BH, Gaynord J, Rowe SM, Deingruber T, Spring DR (2021) The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions. Chem Soc Rev 50:7820–7880. https://doi.org/10.1039/d1cs90109e

    Article  CAS  Google Scholar 

  9. Huan Y, Kong Q, Mou H, Yi H (2020) Antimicrobial Peptides: classification, design, application and research progress in multiple fields. Front Microbiol 11:582779. https://doi.org/10.3389/fmicb.2020.582779

    Article  Google Scholar 

  10. Rima M, Rima M, Fajloun Z, Sabatier JM, Bechinger B, Naas T (2021) Antimicrobial peptides: a potent alternative to antibiotics. Antibiotics 10:1095. https://doi.org/10.3390/antibiotics10091095

    Article  CAS  Google Scholar 

  11. Zhang C, Yang M, Ericsson AC (2019) Antimicrobial peptides: potential application in liver cancer. Front. Microbiol. 10:1257. https://doi.org/10.3389/fmicb.2019.01257

    Article  Google Scholar 

  12. Cesare GBD, Cristy SA, Garsin DA, Lorenz MC (2020) Antimicrobial peptides: a new frontier in antifungal therapy. mBio 11:e02123-20. https://doi.org/10.1128/mBio.02123-20

    Article  Google Scholar 

  13. Fernández de Ullivarri M, Arbulu S, Garcia-Gutierrez E, Cotter PD (2020) Antifungal peptides as therapeutic agents. Front Cell Infect Microbiol 10:105. https://doi.org/10.3389/fcimb.2020.00105

    Article  CAS  Google Scholar 

  14. Mahlapuu M, Björn C, Ekblom J (2020) Antimicrobial peptides as therapeutic agents: opportunities and challenges. Crit Rev Biotechnol 40:978–992. https://doi.org/10.1080/07388551.2020.1796576

    Article  CAS  Google Scholar 

  15. Dijksteel GS, Ulrich MMW, Middelkoop E, Boekema BKHL (2021) Review: lessons learned from clinical trials using antimicrobial peptides (AMPs). Front Microbiol 12:616979. https://doi.org/10.3389/fmicb.2021.616979

    Article  Google Scholar 

  16. Travkova OG, Moehwald H, Brezesinski G (2017) The interaction of antimicrobial peptides with membranes. Adv Colloid Interfac 247:521–532. https://doi.org/10.1016/j.cis.2017.06.001

    Article  CAS  Google Scholar 

  17. Askari P, Namaei MH, Ghazvini K, Hosseini M (2021) In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria. BMC Pharmacol Toxicol 22:42. https://doi.org/10.1186/s40360-021-00503-z

    Article  CAS  Google Scholar 

  18. Gasanoff E, Liu Y, Li F, Hanlon P, Garab G (2021) Bee venom melittin disintegrates the respiration of mitochondria in healthy cells and lymphoblasts, and induces the formation of non-bilayer structures in model inner mitochondrial membranes. Int J Mol Sci 22:11122. https://doi.org/10.3390/ijms222011122

    Article  CAS  Google Scholar 

  19. Tan P, Fu H, Ma X (2021) Design, optimization, and nanotechnology of antimicrobial peptides: from exploration to applications. Nano Today 39:101229. https://doi.org/10.1016/j.nantod.2021.101229

    Article  CAS  Google Scholar 

  20. Zheng J, Li J, Zhang L, Chen X, Yu Y, Huang H (2020) Post-graphene 2D materials-based antimicrobial agents: focus on fabrication strategies and biosafety assessments. J Mater Sci 55:7226–7246. https://doi.org/10.1007/s10853-020-04507-8

    Article  CAS  Google Scholar 

  21. Yang Z, He S, Wu H, Yin T, Wang L, Shan A (2021) Nanostructured antimicrobial peptides: crucial steps of overcoming the bot-tleneck for clinics. Front Microbiol 12:710199. https://doi.org/10.3389/fmicb.2021.710199

    Article  Google Scholar 

  22. Li B, Pan L, Zhang H, Xie L, Wang X, Shou J, Qi Y, Yan X (2021) Recent developments on using nanomaterials to combat Candida albicans. Front Chem 9:813973. https://doi.org/10.3389/fchem.2021.813973

    Article  CAS  Google Scholar 

  23. Andoy NMO, Jeon K, Kreis CT, Sullan RMA (2020) Multifunctional and stimuli-responsive polydopamine nanoparticle-based platform for targeted antimicrobial applications. Adv Funct Mater 30:2004503. https://doi.org/10.1002/adfm.202004503

    Article  CAS  Google Scholar 

  24. Rekha R, Divya M, Govindarajan M, Alharbi NS, Kadaikunnan S, Khaled JM, Al-Anbr MN, Pavela R, Vaseeharan B (2019) Synthesis and characterization of crustin capped titanium dioxide nanoparticles: photocatalytic, antibacterial, antifungal and insecticidal activities. J Photoch Photobio B 199:111620. https://doi.org/10.1016/j.jphotobiol.2019.111620

    Article  CAS  Google Scholar 

  25. Mendes RF, Figueira F, Leite JP, Gales L, Paz FAA (2020) Metal–organic frameworks: a future toolbox for biomedicine? Chem Soc Rev 49:9121–9153. https://doi.org/10.1039/d0cs00883d

    Article  CAS  Google Scholar 

  26. Kirchon A, Feng L, Drake HF, Joseph EA, Zhou H (2018) From fundamentals to applications: a toolbox for robust and multifunctional MOF materials. Chem Soc Rev 47:8611–8638. https://doi.org/10.1039/c8cs00688a

    Article  CAS  Google Scholar 

  27. Yang S, Veerana M, Yu N, Ketya W, Park G, Kim S, Kim Y (2022) Copper(II)-MOF containing glutarate and 4,4′-azopyridine and its antifungal activity. Appl Sci. https://doi.org/10.3390/app12010260

    Article  Google Scholar 

  28. Bouson S, Krittayavathananon A, Phattharasupakun N, Siwayaprahm P, Sawangphruk M (2017) Antifungal activity of water-stable copper-containing metal-organic frameworks. R Soc open sci 4:170654. https://doi.org/10.1098/rsos.170654

    Article  CAS  Google Scholar 

  29. Kirillov AM, Wieczorek SW, Lis A et al (2011) 1,3,5-Triaza-7-phosphaadamantane-7-oxide (PTAdO): New diamondoid building block for design of three-dimensional metal-organic frameworks. Cryst Growth Des 11:2711–2716. https://doi.org/10.1021/cg200571y

    Article  CAS  Google Scholar 

  30. Su L, Li Y, Liu Y et al (2020) Antifungal-inbuilt metal–organic-frameworks eradicate Candida albicans bioflms. Adv Funct Mater 30:2000537. https://doi.org/10.1002/adfm.202000537

    Article  CAS  Google Scholar 

  31. Bai X, Zhang J, Cheng G et al (2022) Dual antibacterial polypeptide-coated PCL@ZIF-8 nanofiber reduces infection and inflammation in burn wounds. J Mater Sci 57:3678–3687. https://doi.org/10.1007/s10853-021-06832-y

    Article  CAS  Google Scholar 

  32. Nie X, Wu S, Huang F, Li W, Qiao H, Wang Q, Wei Q (2021) “Dew-of-leaf” structure multiple synergetic antimicrobial modality hybrid: a rapid and long lasting bactericidal material. Chem Eng J 15:129072. https://doi.org/10.1016/j.cej.2021.129072

    Article  CAS  Google Scholar 

  33. Pettinari C, Pettinari R, Nicola CD, Tombesi A, Scuri S, Marchetti F (2021) Antimicrobial MOFs. Coordin Chem Rev 446:214121. https://doi.org/10.1016/j.ccr.2021.214121

    Article  CAS  Google Scholar 

  34. Li R, Chen T, Pan X (2021) Metal-organic-framework-based materials for antimicrobial applications. ACS Nano 15:3808–3848. https://doi.org/10.1021/acsnano.0c09617

    Article  CAS  Google Scholar 

  35. Polash SA, Khare T, Kumar V, Shukla R (2021) Prospects of exploring the metal-organic framework for combating antimicrobial resistance. ACS Appl Bio Mater 4:8060–8079. https://doi.org/10.1021/acsabm.1c00832

    Article  CAS  Google Scholar 

  36. Zhang Y, Pu C, Tang W, Wang S, Sun Q (2019) Gallic acid liposomes decorated with lactoferrin: characterization, in vitro digestion and antibacterial activity. Food Chem. 293:315–322. https://doi.org/10.1016/j.foodchem.2019.04.116

    Article  CAS  Google Scholar 

  37. Wang H, Chen Y, Wang H, Liu X, Zhou X, Wang F (2019) DNAzyme-loaded metal–organic frameworks (MOFs) for self-sufficient gene therapy. Angew Chem Int Ed 58:7380–7384. https://doi.org/10.1002/anie.201902714

    Article  CAS  Google Scholar 

  38. Finkel JS, Mitchell AP (2011) Genetic control of Candida albicans biofilm development. Nat Rev Microbiol 9:109–118. https://doi.org/10.1038/nrmicro2475

    Article  CAS  Google Scholar 

  39. Wall G, Montelongo-Jauregui D, Bonifacio BV, Lopez-Ribot JL, Uppuluri P (2019) Candida albicans biofilm growth and dispersal: contributions to pathogenesis. Curr Opin Microbiol 52:1–6. https://doi.org/10.1016/j.mib.2019.04.001

    Article  CAS  Google Scholar 

  40. Yu Q, Wang H, Xu N, Cheng X, Wang Y, Zhang B, Xing L, Li M (2012) Spf1 strongly influences calcium homeostasis, hyphal development, biofilm formation and virulence in Candida albicans. Microbiology 158:2272–2282. https://doi.org/10.1099/mic.0.057232-0

    Article  CAS  Google Scholar 

  41. Li Y, Zhang W, Niu J, Chen Y (2012) Mechanism of photogenerated reactive oxygen species and correlation with the antibacterial properties of engineered metal-oxide nanoparticles. ACS Nano 6:5164–5173. https://doi.org/10.1021/nn300934k

    Article  CAS  Google Scholar 

  42. Rowe SE, Wagner NJ, Li L et al (2020) Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection. Nat Microbiol 5:282–290. https://doi.org/10.1038/s41564-019-0627-y

    Article  CAS  Google Scholar 

  43. Kwok ACM, Zhang F, Ma Z, Chan WS, Yu VC, Tsang JSH, Wong JTY (2020) Functional responses between PMP3 small membrane proteins and membrane potential. Environ Microbiol 22:3066–3080. https://doi.org/10.1111/1462-2920.15027

    Article  CAS  Google Scholar 

  44. Askari P, Namaei MH, Ghazvini K, Hosseini M (2021) In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria. BMC Pharmacol Toxico 22:42. https://doi.org/10.1186/s40360-021-00503-z

    Article  CAS  Google Scholar 

  45. Hu J, Liu Z, Yu Q, Ma T (2020) Preparation of reactive oxygen species-responsive antibacterial hydrogels for efficient anti-infection therapy. Mater Lett 263:127254. https://doi.org/10.1016/j.matlet.2019.127254

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by National Natural Science Foundation of China (3217010793, 31870139), and the Fundamental Research Funds for the Central Universities.

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Author notes

  1. Dixiong Yu and Yufan Wang equally contributed to this work and share first authorship.

Authors and Affiliations

  1. Country Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, 300071, People’s Republic of China

    Dixiong Yu, Qilin Yu, Shuo Liu & Mingchun Li

  2. Tianjin Third Central Hospital, Tianjin, 300170, People’s Republic of China

    Yufan Wang

  3. Institute of Agricultural Products Preservation and Processing Technology, Tianjin Academy of Agricultural Sciences, Tianjin, 300384, People’s Republic of China

    Jun Zhang

  4. College of Environmental Science and Engineering, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, Nankai University, 38 Tongyan Rd, Tianjin, 300350, People’s Republic of China

    Shuo Liu

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  1. Dixiong Yu
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Correspondence to Shuo Liu or Mingchun Li.

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All animal experiments were approved by the Animal Care and Use Committee at Nankai University (Approval number 2021-SYDWLL-000023).

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Yu, D., Wang, Y., Zhang, J. et al. Synthesis of the ternary nanocomposites composed of zinc 2-methylimidazolate frameworks, lactoferrin and melittin for antifungal therapy. J Mater Sci 57, 16809–16819 (2022). https://doi.org/10.1007/s10853-022-07672-0

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