Ermes Botte, Pietro Vagaggini, Ilaria Zanoni, Nicole Guazzelli, Lara Faccani, Davide Gardini, Anna L Costa, Arti Ahluwalia
{"title":"Cell-nanoparticle stickiness and dose delivery in a multi-model in silico platform: DosiGUI.","authors":"Ermes Botte, Pietro Vagaggini, Ilaria Zanoni, Nicole Guazzelli, Lara Faccani, Davide Gardini, Anna L Costa, Arti Ahluwalia","doi":"10.1186/s12989-024-00607-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>It is well-known that nanoparticles sediment, diffuse and aggregate when dispersed in a fluid. Once they approach a cell monolayer, depending on the affinity or \"stickiness\" between cells and nanoparticles, they may adsorb instantaneously, settle slowly - in a time- and concentration-dependent manner - or even encounter steric hindrance and rebound. Therefore, the dose perceived by cells in culture may not necessarily be that initially administered. Methods for quantifying delivered dose are difficult to implement, as they require precise characterization of nanoparticles and exposure scenarios, as well as complex mathematical operations to handle the equations governing the system dynamics. Here we present a pipeline and a graphical user interface, DosiGUI, for application to the accurate nano-dosimetry of engineered nanoparticles on cell monolayers, which also includes methods for determining the parameters characterising nanoparticle-cell stickiness.</p><p><strong>Results: </strong>We evaluated the stickiness for 3 industrial nanoparticles (TiO<sub>2</sub> - NM-105, CeO<sub>2</sub> - NM-212 and BaSO<sub>4</sub> - NM-220) administered to 3 cell lines (HepG2, A549 and Caco-2) and subsequently estimated corresponding delivered doses. Our results confirm that stickiness is a function of both nanoparticle and cell type, with the stickiest combination being BaSO<sub>4</sub> and Caco-2 cells. The results also underline that accurate estimations of the delivered dose cannot prescind from a rigorous evaluation of the affinity between the cell type and nanoparticle under investigation.</p><p><strong>Conclusion: </strong>Accurate nanoparticle dose estimation in vitro is crucial for in vivo extrapolation, allowing for their safe use in medical and other applications. This study provides a computational platform - DosiGUI - for more reliable dose-response characterization. It also highlights the importance of cell-nanoparticle stickiness for better risk assessment of engineered nanomaterials.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":7.2000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515606/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Particle and Fibre Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12989-024-00607-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: It is well-known that nanoparticles sediment, diffuse and aggregate when dispersed in a fluid. Once they approach a cell monolayer, depending on the affinity or "stickiness" between cells and nanoparticles, they may adsorb instantaneously, settle slowly - in a time- and concentration-dependent manner - or even encounter steric hindrance and rebound. Therefore, the dose perceived by cells in culture may not necessarily be that initially administered. Methods for quantifying delivered dose are difficult to implement, as they require precise characterization of nanoparticles and exposure scenarios, as well as complex mathematical operations to handle the equations governing the system dynamics. Here we present a pipeline and a graphical user interface, DosiGUI, for application to the accurate nano-dosimetry of engineered nanoparticles on cell monolayers, which also includes methods for determining the parameters characterising nanoparticle-cell stickiness.
Results: We evaluated the stickiness for 3 industrial nanoparticles (TiO2 - NM-105, CeO2 - NM-212 and BaSO4 - NM-220) administered to 3 cell lines (HepG2, A549 and Caco-2) and subsequently estimated corresponding delivered doses. Our results confirm that stickiness is a function of both nanoparticle and cell type, with the stickiest combination being BaSO4 and Caco-2 cells. The results also underline that accurate estimations of the delivered dose cannot prescind from a rigorous evaluation of the affinity between the cell type and nanoparticle under investigation.
Conclusion: Accurate nanoparticle dose estimation in vitro is crucial for in vivo extrapolation, allowing for their safe use in medical and other applications. This study provides a computational platform - DosiGUI - for more reliable dose-response characterization. It also highlights the importance of cell-nanoparticle stickiness for better risk assessment of engineered nanomaterials.
期刊介绍:
Particle and Fibre Toxicology is an online journal that is open access and peer-reviewed. It covers a range of disciplines such as material science, biomaterials, and nanomedicine, focusing on the toxicological effects of particles and fibres. The journal serves as a platform for scientific debate and communication among toxicologists and scientists from different fields who work with particle and fibre materials. The main objective of the journal is to deepen our understanding of the physico-chemical properties of particles, their potential for human exposure, and the resulting biological effects. It also addresses regulatory issues related to particle exposure in workplaces and the general environment. Moreover, the journal recognizes that there are various situations where particles can pose a toxicological threat, such as the use of old materials in new applications or the introduction of new materials altogether. By encompassing all these disciplines, Particle and Fibre Toxicology provides a comprehensive source for research in this field.