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.
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May 2019
Research Article|
May 20 2019
Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property
Vuk Uskoković
;
Vuk Uskoković
1
Department of Bioengineering, University of Illinois
, Chicago, Illinois 60607-70522
Advanced Materials and Nanobiotechnology Laboratory, Department of Biomedical and Pharmaceutical Sciences, Center for Targeted Drug Delivery, Chapman University
, Irvine, California 92618-1908
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Sean Tang;
Sean Tang
2
Advanced Materials and Nanobiotechnology Laboratory, Department of Biomedical and Pharmaceutical Sciences, Center for Targeted Drug Delivery, Chapman University
, Irvine, California 92618-1908
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Marko G. Nikolić;
Marko G. Nikolić
3
Institute of Physics, University of Belgrade
, Pregrevica 118, 11080 Belgrade, Serbia
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Smilja Marković;
Smilja Marković
4
Institute of Technical Sciences of the Serbian Academy of Sciences and Arts (SASA)
, Knez Mihailova 35/IV, 11000 Belgrade, Serbia
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Victoria M. Wu
Victoria M. Wu
2
Advanced Materials and Nanobiotechnology Laboratory, Department of Biomedical and Pharmaceutical Sciences, Center for Targeted Drug Delivery, Chapman University
, Irvine, California 92618-1908
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Biointerphases 14, 031001 (2019)
Article history
Received:
January 27 2019
Accepted:
May 06 2019
Citation
Vuk Uskoković, Sean Tang, Marko G. Nikolić, Smilja Marković, Victoria M. Wu; Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property. Biointerphases 1 May 2019; 14 (3): 031001. https://doi.org/10.1116/1.5090396
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