Helene Kettiger1, Didem Sen Karaman2, Laura Schiesser1, Jessica M Rosenholm3, Jörg Huwyler4. 1. Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland. 2. Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; Laboratory of Physical Chemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland. 3. Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland. 4. Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland. Electronic address: joerg.huwyler@unibas.ch.
Abstract
PURPOSE: Silica nanoparticles (SNPs) are increasingly used as drug delivery systems (DDS) and for biomedical imaging. Therapeutic and diagnostic agents can be incorporated into the silica matrix to improve the stability and dissolution of drug substances in biological systems. However, the safety of SNPs as drug carriers remains controversial. To date, no validated and accepted nano-specific tests exist to predict the potentially harmful impact of these materials on the human body. METHODS: We synthesized by a systematic approach 12 different types of SNPs with varying size, surface topology (porous vs non-porous), and surface modifications. We characterized these particles in terms of dry state and hydrodynamic diameter, specific surface area, and net surface charge (ζ-potential). For cellular studies, we exposed non-phagocytic (HepG2) cells, phagocytic (THP-1) cells, and erythrocytes to SNPs. Cellular uptake and stability of fluorescently labeled SNPs were analyzed by confocal microscopy and flow cytometry. RESULTS: SNPs with a porous surface and negative net surface charge had the strongest impact on cell viability. This is in contrast to non-porous SNPs. None of the studied particles induced oxidative stress in either cell lines. Particles with a negative surface charge induced hemolysis in a concentration-dependent manner. CONCLUSIONS: Physico-chemical properties promoting cytotoxicity and hemolysis were investigated. Our study revealed potential hazards of spherical amorphous SNPs.
PURPOSE:Silica nanoparticles (SNPs) are increasingly used as drug delivery systems (DDS) and for biomedical imaging. Therapeutic and diagnostic agents can be incorporated into the silica matrix to improve the stability and dissolution of drug substances in biological systems. However, the safety of SNPs as drug carriers remains controversial. To date, no validated and accepted nano-specific tests exist to predict the potentially harmful impact of these materials on the human body. METHODS: We synthesized by a systematic approach 12 different types of SNPs with varying size, surface topology (porous vs non-porous), and surface modifications. We characterized these particles in terms of dry state and hydrodynamic diameter, specific surface area, and net surface charge (ζ-potential). For cellular studies, we exposed non-phagocytic (HepG2) cells, phagocytic (THP-1) cells, and erythrocytes to SNPs. Cellular uptake and stability of fluorescently labeled SNPs were analyzed by confocal microscopy and flow cytometry. RESULTS: SNPs with a porous surface and negative net surface charge had the strongest impact on cell viability. This is in contrast to non-porous SNPs. None of the studied particles induced oxidative stress in either cell lines. Particles with a negative surface charge induced hemolysis in a concentration-dependent manner. CONCLUSIONS: Physico-chemical properties promoting cytotoxicity and hemolysis were investigated. Our study revealed potential hazards of spherical amorphous SNPs.
Authors: Massimiliano G Bianchi; Martina Chiu; Giuseppe Taurino; Enrico Bergamaschi; Francesco Cubadda; Guido M Macaluso; Ovidio Bussolati Journal: Nanomaterials (Basel) Date: 2022-07-05 Impact factor: 5.719