PMID- 26434530 OWN - NLM STAT- MEDLINE DCOM- 20161007 LR - 20161230 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 30 IP - 1 Pt B DP - 2015 Dec 25 TI - Comparative safety evaluation of silica-based particles. PG - 355-63 LID - S0887-2333(15)00250-7 [pii] LID - 10.1016/j.tiv.2015.09.030 [doi] AB - 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 (zeta-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. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Kettiger, Helene AU - Kettiger H AD - Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland. FAU - Sen Karaman, Didem AU - Sen Karaman D AD - Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Abo Akademi University, Turku, Finland; Laboratory of Physical Chemistry, Faculty of Science and Engineering, Abo Akademi University, Turku, Finland. FAU - Schiesser, Laura AU - Schiesser L AD - Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland. FAU - Rosenholm, Jessica M AU - Rosenholm JM AD - Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Abo Akademi University, Turku, Finland. FAU - Huwyler, Jorg AU - Huwyler J AD - Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland. Electronic address: joerg.huwyler@unibas.ch. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151003 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 7631-86-9 (Silicon Dioxide) SB - IM MH - Cell Survival/drug effects MH - Drug Delivery Systems MH - Hemolysis/drug effects MH - Hep G2 Cells MH - Humans MH - Nanoparticles/*toxicity MH - Oxidative Stress/drug effects MH - Particle Size MH - Silicon Dioxide/*toxicity OTO - NOTNLM OT - Cell viability OT - Hemolysis OT - Oxidative stress OT - Silica nanoparticles EDAT- 2015/10/06 06:00 MHDA- 2016/10/08 06:00 CRDT- 2015/10/06 06:00 PHST- 2015/04/08 00:00 [received] PHST- 2015/08/13 00:00 [revised] PHST- 2015/09/29 00:00 [accepted] PHST- 2015/10/06 06:00 [entrez] PHST- 2015/10/06 06:00 [pubmed] PHST- 2016/10/08 06:00 [medline] AID - S0887-2333(15)00250-7 [pii] AID - 10.1016/j.tiv.2015.09.030 [doi] PST - ppublish SO - Toxicol In Vitro. 2015 Dec 25;30(1 Pt B):355-63. doi: 10.1016/j.tiv.2015.09.030. Epub 2015 Oct 3.