AMP-Coated TiO <sub>2</sub> Doped ZnO Nanomaterials Enhanced Antimicrobial Activity and Efficacy in Otitis Media Treatment by Elevating Hydroxyl Radical Levels

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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 ₂@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 Staphylococcus aureus ( S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae ( S. pneumoniae) were 10 μg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae 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.

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Nanoparticles: Properties, applications and toxicities

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Endogenous cationic antimicrobial peptides (CAMPs) are among the most ancient and efficient components of host defence. It is somewhat of an enigma that bacteria have not developed highly effective CAMP-resistance mechanisms, such as those that inhibit many therapeutic antibiotics. Here, we propose that CAMPs and CAMP-resistance mechanisms have co-evolved, leading to a transient host-pathogen balance that has shaped the existing CAMP repertoire. Elucidating the underlying principles of this process could help in the development of more sustainable antibiotics.

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Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness.

Threes Smijs, Pavel (2011)

Sunscreens are used to provide protection against adverse effects of ultraviolet (UV)B (290-320 nm) and UVA (320-400 nm) radiation. According to the United States Food and Drug Administration, the protection factor against UVA should be at least one-third of the overall sun protection factor. Titanium dioxide (TiO2) and zinc oxide (ZnO) minerals are frequently employed in sunscreens as inorganic physical sun blockers. As TiO2 is more effective in UVB and ZnO in the UVA range, the combination of these particles assures a broad-band UV protection. However, to solve the cosmetic drawback of these opaque sunscreens, microsized TiO2 and ZnO have been increasingly replaced by TiO2 and ZnO nanoparticles (NPs) (<100 nm). This review focuses on significant effects on the UV attenuation of sunscreens when microsized TiO2 and ZnO particles are replaced by NPs and evaluates physicochemical aspects that affect effectiveness and safety of NP sunscreens. With the use of TiO2 and ZnO NPs, the undesired opaqueness disappears but the required balance between UVA and UVB protection can be altered. Utilization of mixtures of micro- and nanosized ZnO dispersions and nanosized TiO2 particles may improve this situation. Skin exposure to NP-containing sunscreens leads to incorporation of TiO2 and ZnO NPs in the stratum corneum, which can alter specific NP attenuation properties due to particle-particle, particle-skin, and skin-particle-light physicochemical interactions. Both sunscreen NPs induce (photo)cyto- and genotoxicity and have been sporadically observed in viable skin layers especially in case of long-term exposures and ZnO. Photocatalytic effects, the highest for anatase TiO2, cannot be completely prevented by coating of the particles, but silica-based coatings are most effective. Caution should still be exercised when new sunscreens are developed and research that includes sunscreen NP stabilization, chronic exposures, and reduction of NPs' free-radical production should receive full attention.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Nanomedicine

Journal ID (iso-abbrev): Int J Nanomedicine

Journal ID (publisher-id): ijn

Title: International Journal of Nanomedicine

Publisher: Dove

ISSN (Print): 1176-9114

ISSN (Electronic): 1178-2013

Publication date (Electronic): 26 March 2024

Publication date Collection: 2024

Volume: 19

Pages: 2995-3007

Affiliations

[1 ]National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agriculture University , Beijing, People’s Republic of China

[2 ]101 Institute of the Ministry of Civil Affairs , Beijing, People’s Republic of China

[3 ]Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, People’s Republic of China

Author notes

Correspondence: Xuemei Zhou, 101 Institute of the Ministry of Civil Affairs , South Fourth Ring West Road No.188, Beijing, 100070, Email zxmcaur@126.com;

Tianlong Liu, College of Veterinary Medicine, China Agriculture University , Yuanmingyuan West Road No. 2, Beijing, 100193, Email liutianlong@cau.edu.cn

[*]

These authors contributed equally to this work

Article

Publisher ID: 449888

DOI: 10.2147/IJN.S449888

PMC ID: 10981428

PubMed ID: 38559446

SO-VID: 0a441c72-c74a-42e7-b83d-dc0c2376389c

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 14 November 2023

Date accepted : 06 March 2024

Page count

Figures: 6, References: 58, Pages: 13