Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property
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One of the main goals of materials science in the 21st century is the development of materials with rationally designed properties as substitutes for traditional pharmacotherapies. At the same time, there is a lack of understanding of the exact material properties that induce therapeutic effects in biological systems, which limits their rational optimization for the related medical applications. This study sets the foundation for a general approach for elucidating nanoparticle properties as determinants of antibacterial activity, with a particular focus on calcium phosphate nanoparticles. To that end, nine physicochemical effects were studied and a number of them were refuted, thus putting an end to frequently erred hypotheses in the literature. Rather than having one key particle property responsible for eliciting the antibacterial effect, a complex synergy of factors is shown to be at work, including (a) nanoscopic size; (b) elevated intracellular free calcium levels due to nanoparti...cle solubility; (c) diffusivity and favorable electrostatic properties of the nanoparticle surface, primarily low net charge and high charge density; and (d) the dynamics of perpetual exchange of ultrafine clusters across the particle/solution interface. On the positive side, this multifaceted mechanism is less prone to induce bacterial resistance to the therapy and can be a gateway to the sphere of personalized medicine. On a more problematic side, it implies a less intense effect compared to single-target molecular therapies and a difficulty of elucidating the exact mechanisms of action, while also making the rational design of theirs for this type of medical application a challenge.
Кључне речи:
nanoparticles / antimicrobials / calcium phosphateИзвор:
Biointerphases, 2019, 14, 3, 031001-Издавач:
- AIP Publishing LLC
Финансирање / пројекти:
- United States National Institutes of Health (NIH) / National Institute of Dental and Craniofacial Research (NIDCR), Grant K99-DE021416
Напомена:
- This is the peer reviewed version of the following article: Uskoković, V., Tang, S., Nikolić, M.G., Marković, S., Wu, V.M., 2019. Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property. Biointerphases 14, 031001. https://doi.org/10.1116/1.5090396
DOI: 10.1116/1.5090396
ISSN: 1934-8630
WoS: 000468801600001
Scopus: 2-s2.0-85065959658
Институција/група
Институт техничких наука САНУ / Institute of Technical Sciences of SASATY - JOUR AU - Uskoković, Vuk AU - Tang, Sean AU - Nikolić, Marko G. AU - Marković, Smilja AU - Wu, Victoria M. PY - 2019 UR - https://avs.scitation.org/doi/abs/10.1116/1.5090396 UR - https://dais.sanu.ac.rs/123456789/6469 AB - One of the main goals of materials science in the 21st century is the development of materials with rationally designed properties as substitutes for traditional pharmacotherapies. At the same time, there is a lack of understanding of the exact material properties that induce therapeutic effects in biological systems, which limits their rational optimization for the related medical applications. This study sets the foundation for a general approach for elucidating nanoparticle properties as determinants of antibacterial activity, with a particular focus on calcium phosphate nanoparticles. To that end, nine physicochemical effects were studied and a number of them were refuted, thus putting an end to frequently erred hypotheses in the literature. Rather than having one key particle property responsible for eliciting the antibacterial effect, a complex synergy of factors is shown to be at work, including (a) nanoscopic size; (b) elevated intracellular free calcium levels due to nanoparticle solubility; (c) diffusivity and favorable electrostatic properties of the nanoparticle surface, primarily low net charge and high charge density; and (d) the dynamics of perpetual exchange of ultrafine clusters across the particle/solution interface. On the positive side, this multifaceted mechanism is less prone to induce bacterial resistance to the therapy and can be a gateway to the sphere of personalized medicine. On a more problematic side, it implies a less intense effect compared to single-target molecular therapies and a difficulty of elucidating the exact mechanisms of action, while also making the rational design of theirs for this type of medical application a challenge. PB - AIP Publishing LLC T2 - Biointerphases T1 - Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property SP - 031001 VL - 14 IS - 3 DO - 10.1116/1.5090396 UR - https://hdl.handle.net/21.15107/rcub_dais_6469 ER -
@article{ author = "Uskoković, Vuk and Tang, Sean and Nikolić, Marko G. and Marković, Smilja and Wu, Victoria M.", year = "2019", abstract = "One of the main goals of materials science in the 21st century is the development of materials with rationally designed properties as substitutes for traditional pharmacotherapies. At the same time, there is a lack of understanding of the exact material properties that induce therapeutic effects in biological systems, which limits their rational optimization for the related medical applications. This study sets the foundation for a general approach for elucidating nanoparticle properties as determinants of antibacterial activity, with a particular focus on calcium phosphate nanoparticles. To that end, nine physicochemical effects were studied and a number of them were refuted, thus putting an end to frequently erred hypotheses in the literature. Rather than having one key particle property responsible for eliciting the antibacterial effect, a complex synergy of factors is shown to be at work, including (a) nanoscopic size; (b) elevated intracellular free calcium levels due to nanoparticle solubility; (c) diffusivity and favorable electrostatic properties of the nanoparticle surface, primarily low net charge and high charge density; and (d) the dynamics of perpetual exchange of ultrafine clusters across the particle/solution interface. On the positive side, this multifaceted mechanism is less prone to induce bacterial resistance to the therapy and can be a gateway to the sphere of personalized medicine. On a more problematic side, it implies a less intense effect compared to single-target molecular therapies and a difficulty of elucidating the exact mechanisms of action, while also making the rational design of theirs for this type of medical application a challenge.", publisher = "AIP Publishing LLC", journal = "Biointerphases", title = "Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property", pages = "031001", volume = "14", number = "3", doi = "10.1116/1.5090396", url = "https://hdl.handle.net/21.15107/rcub_dais_6469" }
Uskoković, V., Tang, S., Nikolić, M. G., Marković, S.,& Wu, V. M.. (2019). Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property. in Biointerphases AIP Publishing LLC., 14(3), 031001. https://doi.org/10.1116/1.5090396 https://hdl.handle.net/21.15107/rcub_dais_6469
Uskoković V, Tang S, Nikolić MG, Marković S, Wu VM. Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property. in Biointerphases. 2019;14(3):031001. doi:10.1116/1.5090396 https://hdl.handle.net/21.15107/rcub_dais_6469 .
Uskoković, Vuk, Tang, Sean, Nikolić, Marko G., Marković, Smilja, Wu, Victoria M., "Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property" in Biointerphases, 14, no. 3 (2019):031001, https://doi.org/10.1116/1.5090396 ., https://hdl.handle.net/21.15107/rcub_dais_6469 .