AMP-Coated TiO Doped ZnO Nanomaterials Enhanced Antimicrobial Activity and Efficacy in Otitis Media Treatment by Elevating Hydroxyl Radical Levels.

Qianyu Bai, Yichi Zhang, Runqiu Cai, Haiyan Wu, Huiqun Fu, Xuemei Zhou, Jie Chai, Xuepeng Teng, Tianlong Liu
Author Information
  1. Qianyu Bai: National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agriculture University, Beijing, People's Republic of China.
  2. Yichi Zhang: National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agriculture University, Beijing, People's Republic of China.
  3. Runqiu Cai: National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agriculture University, Beijing, People's Republic of China.
  4. Haiyan Wu: National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agriculture University, Beijing, People's Republic of China.
  5. Huiqun Fu: 101 Institute of the Ministry of Civil Affairs, Beijing, People's Republic of China.
  6. Xuemei Zhou: 101 Institute of the Ministry of Civil Affairs, Beijing, People's Republic of China.
  7. Jie Chai: Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China.
  8. Xuepeng Teng: Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China.
  9. Tianlong Liu: National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agriculture University, Beijing, People's Republic of China.

Abstract

Background: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed.
Methods: ZnO@TiO@AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs.
Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against (), methicillin-resistant (MRSA), and () were 10 μg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against , and were 50 μg/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (·OH) compared to ZnO NPs.
Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.

Keywords

References

  1. Nanomaterials (Basel). 2020 Oct 01;10(10): [PMID: 33019690]
  2. Infect Drug Resist. 2023 Feb 28;16:1203-1219 [PMID: 36879855]
  3. Adv Drug Deliv Rev. 2021 Nov;178:113973 [PMID: 34530014]
  4. ACS Biomater Sci Eng. 2020 Apr 13;6(4):2038-2049 [PMID: 33455322]
  5. Antibiotics (Basel). 2023 Jan 30;12(2): [PMID: 36830185]
  6. Nat Rev Microbiol. 2006 Jul;4(7):529-36 [PMID: 16778838]
  7. Biomater Sci. 2020 Mar 31;8(7):2031-2039 [PMID: 32083626]
  8. ACS Appl Mater Interfaces. 2015 Jan 21;7(2):1308-17 [PMID: 25537255]
  9. Nanoscale. 2022 May 16;14(18):6709-6734 [PMID: 35475489]
  10. Sci China Life Sci. 2020 Aug;63(8):1168-1182 [PMID: 32458255]
  11. Drug Resist Updat. 2023 May;68:100954 [PMID: 36905712]
  12. Nanomaterials (Basel). 2023 Jun 04;13(11): [PMID: 37299703]
  13. FEBS J. 2009 Nov;276(22):6483-96 [PMID: 19817856]
  14. J Biomed Mater Res A. 2015 Jul;103(7):2499-507 [PMID: 25530348]
  15. Vaccine. 2008 Mar 17;26(12):1501-24 [PMID: 18295938]
  16. Nanomedicine. 2021 Jun;34:102381 [PMID: 33771705]
  17. Chem Commun (Camb). 2022 Jan 13;58(5):607-618 [PMID: 34950943]
  18. J Biophotonics. 2017 Mar;10(3):394-403 [PMID: 27009636]
  19. Asian J Pharm Sci. 2020 Jan;15(1):42-59 [PMID: 32175017]
  20. Chem Commun (Camb). 2009 Jul 21;(27):4034-6 [PMID: 19568624]
  21. Curr Opin Crit Care. 2023 Oct 1;29(5):438-445 [PMID: 37641512]
  22. Nanotechnol Sci Appl. 2011 Oct 13;4:95-112 [PMID: 24198489]
  23. Antibiotics (Basel). 2021 Jul 20;10(7): [PMID: 34356805]
  24. J Infect Dis. 2011 Jan 15;203(2):273-82 [PMID: 21288828]
  25. J Coat Technol Res. 2023;20(3):789-817 [PMID: 36777289]
  26. Mater Sci Eng C Mater Biol Appl. 2021 Feb;121:111843 [PMID: 33579480]
  27. Int J Mol Sci. 2021 Oct 22;22(21): [PMID: 34768832]
  28. ACS Appl Mater Interfaces. 2022 Aug 3;14(30):34527-34537 [PMID: 35875986]
  29. Environ Pollut. 2016 Nov;218:863-869 [PMID: 27524254]
  30. Protein Cell. 2010 Feb;1(2):143-52 [PMID: 21203984]
  31. Molecules. 2020 May 09;25(9): [PMID: 32397569]
  32. Front Genet. 2019 Nov 26;10:1230 [PMID: 31850076]
  33. Infect Drug Resist. 2023 Aug 14;16:5295-5308 [PMID: 37601564]
  34. J Mater Chem B. 2021 Feb 15;9(5):1189-1207 [PMID: 33406200]
  35. Microbiol Mol Biol Rev. 2023 Jun 28;87(2):e0003722 [PMID: 37129495]
  36. Int J Mol Sci. 2022 Jun 17;23(12): [PMID: 35743214]
  37. Nanomedicine. 2018 Feb;14(2):365-372 [PMID: 29170111]
  38. Pharmaceutics. 2022 Sep 27;14(10): [PMID: 36297497]
  39. Curr Pharm Des. 2023;29(5):312-322 [PMID: 36717996]
  40. Nanomaterials (Basel). 2023 Mar 08;13(6): [PMID: 36985872]
  41. Pestic Biochem Physiol. 2021 Jul;176:104869 [PMID: 34119214]
  42. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2014;31(2):173-86 [PMID: 24219062]
  43. Front Pharmacol. 2021 Aug 04;12:640514 [PMID: 34421583]
  44. Int J Audiol. 2003 Mar;42(2):89-105 [PMID: 12641392]

MeSH Term

Humans
Methicillin-Resistant Staphylococcus aureus
Staphylococcus aureus
Hydroxyl Radical
Zinc Oxide
Anti-Bacterial Agents
Staphylococcal Infections
Otitis Media
Microbial Sensitivity Tests
Metal Nanoparticles

Chemicals

Hydroxyl Radical
Zinc Oxide
Anti-Bacterial Agents

Word Cloud

Created with Highcharts 10.0.0NPsATZotitismediaantimicrobialvitrovivoantibacterialhydroxylZnObiocompatibilityEPRradicalsexhibitedMinimumConcentrationvalueμg/mLtreatmentBackground:pastdecadesresistanceAMRmajorthreatglobalpublichealthLong-termchronicbecomingchallengingtreatthusnovelantibioticalternativeagentsmuchneededMethods:ZnO@TiO@AMPsynthesizedsolvothermalmethodsubjectedcomprehensivecharacterizationeffectevaluatedmechanismexplorationutilizedElectronParamagneticResonanceSpectrometerdetectanalyzeproducedResults:sphericalstructure9985nmdrug-loadingrate2073%AMPwithin4186%NotablyInhibitoryMICmethicillin-resistantMRSA10BactericidalMBC50comparisonmodelgroupsignificantlyreducesinflammatoryexudationmiddleearcavityobservabledamagetympanicmembranetoxicitytestsindicatinggoodMoreoverspectroscopyresultshighlightedsuperiorabilitygenerate·OHcomparedConclusion:remarkablepropertiesinnovativeapplicationadvancedbringinggreatpromiseAMP-CoatedTiODopedNanomaterialsEnhancedAntimicrobialActivityEfficacyOtitisMediaTreatmentElevatingHydroxylRadicalLevelspeptideradicalmesoporoustitaniumdioxidenanoparticleszincoxide

Similar Articles

Cited By