NanoPASS: an easy-to-use user interface for nanoparticle dosimetry with the 3DSDD model

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(2020) 17:45

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NanoPASS: an easy-to-use user interface for nanoparticle dosimetry with the 3DSDD model Falko Frenzel1 , Laura König-Mattern2, Valerie Stock1, Linn Voss1, Maxi B. Paul1, Holger Sieg1 , Albert Braeuning1, Andreas Voigt2 and Linda Böhmert1*

Abstract Nanoparticles exhibit a specific diffusion and sedimentation behavior under cell culture conditions as used in nantoxicological in vitro testing. How a particular particle suspension behaves depends on the particular physicochemical characteristics of the particles and the cell culture system. Only a fraction of the nanoparticles applied to a cell culture will thus reach the cells within a given time frame. Therefore, dosimetric calculations are essential not only to determine the exact fraction of nanoparticles that has come into contact with the cells, but also to ensure experimental comparability and correct interpretation of results, respectively. Yet, the use of published dosimetry models is limited. Not the least because the correct application of these in silico tools usually requires bioinformatics knowledge, which often is perceived a hurdle. Moreover, not all models are freely available and accessible. In order to overcome this obstacle, we have now developed an easy-to-use interface for our recently published 3DSDD dosimetry model, called NanoPASS (NanoParticle Administration Sedimentation Simulator). The interface is freely available to all researchers. It will facilitate the use of in silico dosimetry in nanotoxicology and thus improve interpretation and comparability of in vitro results in the field. Keywords: Dosimetric calculation, Nanotoxicology, In vitro, Cell culture, Caco-2, HepaRG

Introduction The number of in vitro studies on particle uptake, effects and toxicity is increasing. While the main focus of toxicological research has been in the field of inorganic nanoparticles, plastic particles, especially microplastics, have recently also come into focus [2]. Small-sized particles differ by size, shape, surface coating and agglomeration behavior, and show a particular behavior with respect to their concentration distribution in dispersion: within a given time frame, only a fraction of the applied particles will come into contact with cells located at the bottom of a cell culture vessel [10, 11]. This fraction, * Correspondence: [email protected] 1 German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany Full list of author information is available at the end of the article

termed “effective dose”, “delivered dose” or “target cell dose” depends on the physicochemical characteristics of the particles and of the liquid, e.g. the cell culture medium. Together, these characteristics determine how sedimentation and diffusion affect particle distribution over time [3, 12, 13]. Dosimetry, i.e. the determination of the effective dose of particles that have come into contact with cells in in vitro experiments, is a major issue in the field of particle t