NYCSEA

Abstract: 

Antibiotic resistance has been a growing challenge to the effective management of infected chronic wounds. Recently, photodynamic therapy (PDT) has shown promise as a treatment for killing bacteria or causing cell death by producing reactive oxygen species (ROS) directly at the site of infection. However, there is a challenge known as the oxidative stress dilemma in which a high level of ROS needs to be generated to achieve efficient bacterial killing. Too much oxidative stress is harmful to the normal tissue surrounding the wound site and leads to inflammation. Therefore, this work aims to create nanoparticles that are sensitive to light and have anti-inflammatory properties, along with other specially designed functions.

Before carrying out the computational experiment, we investigated the influence of nanomodulators on biofilms. Since then, we have created metal oxide nanoparticles, which have been altered by the functional groups. Upon biofilm exposure, the excess superoxide induced by metal oxides is quantitatively converted into a low concentration of product. The bactericidal effect on biofilms is conserved, while the concentration of superoxide, which is highly harmful to eukaryotic cells, is strongly decreased. Iridium-based nanoparticles were also modeled and analyzed, as these groups have been shown to be highly efficient in eradicating biofilms through photodynamic therapy when activated by near-infrared light. When exposed to light, the nanoclusters act like antioxidant enzymes, removing excess ROS and reducing inflammation, which helps the tissue heal faster.

In this paper, analytical chemistry and molecular editing programs such as Avogadro and Gaussian with an auto-optimization feature were employed. The tools calculated the theoretical values of a molecule’s physicochemical properties that were used to model the nanoscale compounds. The programs enable us to build virtual biochemical compounds, and we were able to find the thermodynamic stability, activity of the compounds, and other quantum chemical parameters.

References

1. Hamblin, M. R., & Hasan, T. (2004). Photodynamic therapy: A new antimicrobial approach to infectious disease? Photochemical & Photobiological Sciences, 3(5), 436–450. DOI: 10.1039/B311900A
2. Wainwright, M., Maisch, T., Nonell, S., Plaetzer, K., Almeida, A., Tegos, G. P., & Hamblin, M. R. (2017). Photoantimicrobials—Are we afraid of the light? The Lancet Infectious Diseases, 17(2), e49–e55. DOI: 10.1016/S1473-3099(16)30268-7
3. Abrahamse, H., & Hamblin, M. R. (2016). New photosensitizers for photodynamic therapy. Biochemical Journal, 473(4), 347–364. DOI: 10.1042/BJ20150942
4. Bjarnsholt, T., Kirketerp-Møller, K., Jensen, P. Ø., et al. (2008). Why chronic wounds will not heal: A novel hypothesis. Wound Repair and Regeneration, 16(1), 2–10. DOI: 10.1111/j.1524-475X.2007.00283.x
5. Costerton, J. W., Stewart, P. S., & Greenberg, E. P. (1999). Bacterial biofilms: A common cause of persistent infections. Science, 284(5418), 1318–1322. DOI: 10.1126/science.284.5418.1318
6. Halliwell, B., & Gutteridge, J. M. C. (2015). Free radicals in biology and medicine (5th ed.). Oxford University Press. ISBN: 9780198717485
7. Winterbourn, C. C. (2014). The biological chemistry of hydrogen peroxide. Methods in Enzymology, 528, 3–25. DOI: 10.1016/B978-0-12-405881-1.00001-X
8. Dizaj, S. M., Lotfipour, F., Barzegar-Jalali, M., Zarrintan, M. H., & Adibkia, K. (2014). Antimicrobial activity of metal oxide nanoparticles. Materials Science and Engineering C, 44, 278–284. DOI: 10.1016/j.msec.2014.08.031
9. Khan, I., Saeed, K., & Khan, I. (2019). Nanoparticles: Properties, applications and toxicities. Arabian Journal of Chemistry, 12(7), 908–931. DOI: 10.1016/j.arabjc.2017.05.011
10. Wei, H., & Wang, E. (2013). Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artificial enzymes. Chemical Society Reviews, 42(14), 6060–6093. DOI: 10.1039/C3CS35486E
11. Huang, Y., Ren, J., & Qu, X. (2019). Nanozymes: Classification, catalytic mechanisms, activity regulation, and applications. Chemical Reviews, 119(6), 4357–4412. DOI: 10.1021/acs.chemrev.8b00672
12. Hanwell, M. D., Curtis, D. E., Lonie, D. C., Vandermeersch, T., Zurek, E., & Hutchison, G. R. (2012). Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. Journal of Cheminformatics, 4, 17. DOI: 10.1186/1758-2946-4-17
13. Frisch, M. J., Trucks, G. W., Schlegel, H. B., et al. (2016). Gaussian 16 Revision C.01. Gaussian, Inc., Wallingford, CT.
14. Parr, R. G., & Yang, W. (1989). Density-Functional Theory of Atoms and Molecules. Oxford University Press. ISBN: 9780195092769
15. Becke, A. D. (1993). Density-functional thermochemistry. III. The role of exact exchange. Journal of Chemical Physics, 98(7), 5648–5652. DOI: 10.1063/1.464913