TY - JOUR
T1 - Functionalization of Silica Nanoparticles for Tailored Interactions with Intestinal Cells and Chemical Modulation of Paracellular Permeability
AU - Iriarte-Mesa, Claudia
AU - Bergen, Janice
AU - Danielyan, Kristina
AU - Crudo, Francesco
AU - Marko, Doris
AU - Kählig, Hanspeter
AU - Del Favero, Giorgia
AU - Kleitz, Freddy
N1 - Publisher Copyright:
© 2024 The Author(s). Small Science published by Wiley-VCH GmbH.
Accession Number
WOS:001281981900001
PY - 2024
Y1 - 2024
N2 - The intestinal compartment confines the gut microbiome while enabling food passage and absorption of active molecules. For the rational design of oral formulations aiming to overcome physiological barriers of the gut, it is crucial to understand how cells respond to the presence of nanoparticulate materials. Taking advantage of the versatility and biocompatibility of dendritic mesoporous silica nanoparticles (DMSNs), several post-grafting strategies are developed to diversify the surface properties of spherical DMSNs and then probe interactions with the intestinal coculture cell model Caco-2/HT29-MTX-E12. Herein, the functionalization of DMSNs with polyethylene glycol, phosphonate, methyl, and farnesol moieties enables the investigation of both particle penetration through the mucus layer and pathways relevant to intracellular uptake. Contributions of surface chemistry, charge, and colloidal stability are correlated with the modulation of particle movement through the mucus and the organization of cell–cell junctions. Hydrophilic and negative functionalities favor particle distribution toward the intestinal monolayer. Instead, hydrophobic DMSNs are hindered by the mucus, possibly limiting cell contact. Hybrid surfaces, combining phosphonate and long carbon chain functions, support diffusion through the mucus and foster the paracellular permeability as well as the transient barrier relapse, as indicated by increased cell–cell distances and reorganization of tight junctions.
AB - The intestinal compartment confines the gut microbiome while enabling food passage and absorption of active molecules. For the rational design of oral formulations aiming to overcome physiological barriers of the gut, it is crucial to understand how cells respond to the presence of nanoparticulate materials. Taking advantage of the versatility and biocompatibility of dendritic mesoporous silica nanoparticles (DMSNs), several post-grafting strategies are developed to diversify the surface properties of spherical DMSNs and then probe interactions with the intestinal coculture cell model Caco-2/HT29-MTX-E12. Herein, the functionalization of DMSNs with polyethylene glycol, phosphonate, methyl, and farnesol moieties enables the investigation of both particle penetration through the mucus layer and pathways relevant to intracellular uptake. Contributions of surface chemistry, charge, and colloidal stability are correlated with the modulation of particle movement through the mucus and the organization of cell–cell junctions. Hydrophilic and negative functionalities favor particle distribution toward the intestinal monolayer. Instead, hydrophobic DMSNs are hindered by the mucus, possibly limiting cell contact. Hybrid surfaces, combining phosphonate and long carbon chain functions, support diffusion through the mucus and foster the paracellular permeability as well as the transient barrier relapse, as indicated by increased cell–cell distances and reorganization of tight junctions.
KW - differentiated intestinal cells
KW - membrane permeation
KW - mesoporous silica nanoparticles
KW - mucus barrier
KW - surface functions
KW - tight junction proteins
UR - http://www.scopus.com/inward/record.url?scp=85200136716&partnerID=8YFLogxK
U2 - 10.1002/smsc.202400112
DO - 10.1002/smsc.202400112
M3 - Article
AN - SCOPUS:85200136716
JO - Small Science
JF - Small Science
ER -