PMID- 35854319 OWN - NLM STAT- MEDLINE DCOM- 20220721 LR - 20220802 IS - 1743-8977 (Electronic) IS - 1743-8977 (Linking) VI - 19 IP - 1 DP - 2022 Jul 19 TI - Changes of physico-chemical properties of nano-biomaterials by digestion fluids affect the physiological properties of epithelial intestinal cells and barrier models. PG - 49 LID - 10.1186/s12989-022-00491-w [doi] LID - 49 AB - BACKGROUND: The widespread use of nano-biomaterials (NBMs) has increased the chance of human exposure. Although ingestion is one of the major routes of exposure to NBMs, it is not thoroughly studied to date. NBMs are expected to be dramatically modified following the transit into the oral-gastric-intestinal (OGI) tract. How these transformations affect their interaction with intestinal cells is still poorly understood. NBMs of different chemical nature-lipid-surfactant nanoparticles (LSNPs), carbon nanoparticles (CNPs), surface modified Fe(3)O(4) nanoparticles (FNPs) and hydroxyapatite nanoparticles (HNPs)-were treated in a simulated human digestive system (SHDS) and then characterised. The biological effects of SHDS-treated and untreated NBMs were evaluated on primary (HCoEpiC) and immortalised (Caco-2, HCT116) epithelial intestinal cells and on an intestinal barrier model. RESULTS: The application of the in vitro SDHS modified the biocompatibility of NBMs on gastrointestinal cells. The differences between SHDS-treated and untreated NBMs could be attributed to the irreversible modification of the NBMs in the SHDS. Aggregation was detected for all NBMs regardless of their chemical nature, while pH- or enzyme-mediated partial degradation was detected for hydroxyapatite or polymer-coated iron oxide nanoparticles and lipid nanoparticles, respectively. The formation of a bio-corona, which contains proteases, was also demonstrated on all the analysed NBMs. In viability assays, undifferentiated primary cells were more sensitive than immortalised cells to digested NBMs, but neither pristine nor treated NBMs affected the intestinal barrier viability and permeability. SHDS-treated NBMs up-regulated the tight junction genes (claudin 3 and 5, occludin, zonula occludens 1) in intestinal barrier, with different patterns between each NBM, and increase the expression of both pro- and anti-inflammatory cytokines (IL-1beta, TNF-alpha, IL-22, IL-10). Notably, none of these NBMs showed any significant genotoxic effect. CONCLUSIONS: Overall, the results add a piece of evidence on the importance of applying validated in vitro SHDS models for the assessment of NBM intestinal toxicity/biocompatibility. We propose the association of chemical and microscopic characterization, SHDS and in vitro tests on both immortalised and primary cells as a robust screening pipeline useful to monitor the changes in the physico-chemical properties of ingested NBMs and their effects on intestinal cells. CI - (c) 2022. The Author(s). FAU - Antonello, Giulia AU - Antonello G AD - Department of Chemistry, University of Turin, Via Pietro Giuria 7, 10125, Turin, Italy. AD - Department of Public Health and Pediatrics, University of Turin, Piazza Polonia, 94, 10126, Turin, Italy. AD - Department of Oncology, University of Turin, Via Santena 5 bis, 10126, Turin, Italy. FAU - Marucco, Arianna AU - Marucco A AD - Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123, Turin, Italy. FAU - Gazzano, Elena AU - Gazzano E AD - Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123, Turin, Italy. FAU - Kainourgios, Panagiotis AU - Kainourgios P AD - Research Unit of Advanced, Composite, Nano-Materials and Nanotechnology, School of Chemical Engineering, National Technical University of Athens, 9 Heroon Polytechniou St., 15780, Zographos, Athens, Greece. FAU - Ravagli, Costanza AU - Ravagli C AD - Colorobbia Consulting Srl, Headwork, Via Pietramarina, 53, 50059, Sovigliana, Vinci, FI, Italy. FAU - Gonzalez-Paredes, Ana AU - Gonzalez-Paredes A AD - Nanovector Srl, Headwork, Via Livorno 60, 10144, Turin, Italy. FAU - Sprio, Simone AU - Sprio S AD - National Research Council, Institute of Science and Technology for Ceramics ISTEC-CNR, Via Granarolo 64, 48018, Faenza, RA, Italy. FAU - Padin-Gonzalez, Esperanza AU - Padin-Gonzalez E AD - Department of Chemistry, Royal College of Surgeons in Ireland (RCSI), 123 St Stephen Green, Dublin 2, Ireland. FAU - Soliman, Mahmoud G AU - Soliman MG AD - Department of Chemistry, Royal College of Surgeons in Ireland (RCSI), 123 St Stephen Green, Dublin 2, Ireland. FAU - Beal, David AU - Beal D AD - CEA, CNRS, IRIG, SyMMES-CIBEST, Universite Grenoble Alpes, 38000, Grenoble, France. FAU - Barbero, Francesco AU - Barbero F AD - Department of Chemistry, University of Turin, Via Pietro Giuria 7, 10125, Turin, Italy. FAU - Gasco, Paolo AU - Gasco P AD - Nanovector Srl, Headwork, Via Livorno 60, 10144, Turin, Italy. FAU - Baldi, Giovanni AU - Baldi G AD - Colorobbia Consulting Srl, Headwork, Via Pietramarina, 53, 50059, Sovigliana, Vinci, FI, Italy. FAU - Carriere, Marie AU - Carriere M AD - CEA, CNRS, IRIG, SyMMES-CIBEST, Universite Grenoble Alpes, 38000, Grenoble, France. FAU - Monopoli, Marco P AU - Monopoli MP AD - Department of Chemistry, Royal College of Surgeons in Ireland (RCSI), 123 St Stephen Green, Dublin 2, Ireland. FAU - Charitidis, Costas A AU - Charitidis CA AD - Research Unit of Advanced, Composite, Nano-Materials and Nanotechnology, School of Chemical Engineering, National Technical University of Athens, 9 Heroon Polytechniou St., 15780, Zographos, Athens, Greece. FAU - Bergamaschi, Enrico AU - Bergamaschi E AD - Department of Public Health and Pediatrics, University of Turin, Piazza Polonia, 94, 10126, Turin, Italy. FAU - Fenoglio, Ivana AU - Fenoglio I AD - Department of Chemistry, University of Turin, Via Pietro Giuria 7, 10125, Turin, Italy. ivana.fenoglio@unito.it. FAU - Riganti, Chiara AU - Riganti C AD - Department of Oncology, University of Turin, Via Santena 5 bis, 10126, Turin, Italy. chiara.riganti@unito.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220719 PL - England TA - Part Fibre Toxicol JT - Particle and fibre toxicology JID - 101236354 RN - 0 (Biocompatible Materials) RN - 0 (Hydroxyapatites) RN - 0 (Lipid Nanoparticles) RN - 0 (Liposomes) SB - IM MH - *Biocompatible Materials/pharmacology MH - Caco-2 Cells MH - Digestion MH - Humans MH - Hydroxyapatites/pharmacology MH - *Intestinal Mucosa MH - Liposomes MH - Nanoparticles MH - Permeability MH - Tight Junctions PMC - PMC9297619 OTO - NOTNLM OT - Biotransformation OT - Caco-2 OT - Gastro-intestinal barrier OT - HCT116 OT - HCoEpiC OT - In vitro simulated digestion OT - Inflammation OT - Nano-biomaterials OT - Permeability OT - Toxicity COIS- The authors declare that they have no competing interests. EDAT- 2022/07/20 06:00 MHDA- 2022/07/22 06:00 PMCR- 2022/07/19 CRDT- 2022/07/19 23:47 PHST- 2022/02/09 00:00 [received] PHST- 2022/06/29 00:00 [accepted] PHST- 2022/07/19 23:47 [entrez] PHST- 2022/07/20 06:00 [pubmed] PHST- 2022/07/22 06:00 [medline] PHST- 2022/07/19 00:00 [pmc-release] AID - 10.1186/s12989-022-00491-w [pii] AID - 491 [pii] AID - 10.1186/s12989-022-00491-w [doi] PST - epublish SO - Part Fibre Toxicol. 2022 Jul 19;19(1):49. doi: 10.1186/s12989-022-00491-w.