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Effect of Hydroxyapatite Nanoparticle Crystallinity and Colloidal Stability on Cytotoxicity
Lea Andrée1, Lucas S Joziasse1, Merel J W Adjobo-Hermans2
1Department of Dentistry-Regenerative Biomaterials, Radboud University Medical Center, Nijmegen 6525 EX, The Netherlands.
ACS Biomaterials Science & Engineering
|October 7, 2024
Summary
Hydroxyapatite nanoparticles (nHA) can be cytotoxic. Agglomeration of nHA increases cytotoxicity more than crystallinity, impacting reactive oxygen species production and guiding future biomedical designs.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cell Biology
Background:
- Hydroxyapatite nanoparticles (nHA) show promise for intracellular drug delivery due to biomolecule binding and pH-dependent solubility.
- Existing research on nHA cytocompatibility presents conflicting results, hindering a clear understanding of cytotoxicity drivers.
- Physicochemical properties like size, shape, crystallinity, and aggregation state are suspected factors in nHA cytotoxicity.
Purpose of the Study:
- To investigate the hypothesis that intracellular calcium levels are the primary driver of nHA nanoparticle cytotoxicity.
- To elucidate the impact of nHA crystallinity and dispersity on cytotoxicity.
- To determine the dominant factor influencing nHA-induced cytotoxicity: crystallinity or agglomeration.
Main Methods:
- Investigated the cytotoxicity of spherical nHA with varying crystallinity and dispersity.
- Quantified intracellular calcium levels following nHA nanoparticle internalization.
- Assessed the production of reactive oxygen species (ROS) in response to nHA exposure.
Main Results:
- Both lower nHA crystallinity and increased agglomeration were found to elevate cytotoxicity.
- Nanoparticle agglomeration emerged as a more significant factor in driving cytotoxicity than crystallinity.
- nHA internalization led to increased intracellular calcium and ROS production, though calcium level changes were subtle.
Conclusions:
- nHA agglomeration is a key factor that enhances ROS production and subsequent cytotoxicity.
- Controlling nHA crystallinity and, particularly, agglomeration is crucial for optimizing biocompatibility in biomedical applications.
- These findings offer essential guidance for the development of safer and more effective nHA-based formulations.
