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Difference in Endocytosis Pathways Used by Differentiated Versus Nondifferentiated Epithelial Caco-2 Cells to Internalize Nanosized Particles
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Researchers compared how differentiated and nondifferentiated intestinal epithelial cells internalize nanosized particles, finding that the two cell types use fundamentally different uptake pathways. Differentiated cells relied primarily on clathrin-mediated endocytosis, while nondifferentiated cells used a broader range of internalization routes. The study highlights the importance of using appropriate cell models when studying how nanoparticles and nanoplastics interact with the gut lining.
Understanding the internalization of nanosized particles by mucosal epithelial cells is essential in a number of areas including viral entry at mucosal surfaces, nanoplastic pollution, as well as design and development of nanotechnology-type medicines. Here, we report our comparative study on pathways of cellular internalization in epithelial Caco-2 cells cultured in vitro as either a polarized, differentiated cell layer or as nonpolarized, nondifferentiated cells. The study reveals a number of differences in the extent that endocytic processes are used by cells, depending on their differentiation status and the nature of applied nanoparticles. In polarized cells, actin-driven and dynamin-independent macropinocytosis plays a prominent role in the internalization of both positively and negatively charged nanoparticles, contrary to its modest contribution in nonpolarized cells. Clathrin-mediated cellular entry plays a prominent role in the endocytosis of positive nanoparticles and cholesterol inhibition in negative nanoparticles. However, in nonpolarized cells, dynamin-dependent endocytosis is a major pathway in the internalization of both positive and negative nanoparticles. Cholesterol depletion affects both nonpolarized and polarized cells' internalization of positive and negative nanoparticles, which, in addition to the effect of cholesterol-binding inhibitors on the internalization of negative nanoparticles, indicates the importance of membrane cholesterol in endocytosis. The data collectively provide a new contribution to understanding endocytic pathways in epithelial cells, particularly pointing to the importance of the cell differentiation stage and the nature of the cargo.
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Nanoparticle Uptake and Crossing by Human In Vitro Models of Intestinal Barriers: A Scoping Review
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This review rounds up what scientists have learned from lab-grown models of the human gut lining, which are used to study how tiny particles, including nanoplastics, metal particles, and fibers we might swallow from food or water, get absorbed into our bodies. The takeaway is that newer, more realistic gut models (which include mucus and different cell types, unlike older simpler versions) are giving us better insight into whether these particles cross into our bloodstream and how they might affect gut health. This matters because as microplastics and nanoparticles become more common in our food and environment, understanding how our intestines handle them is key to figuring out any potential health risks.
Size-Dependent Internalization of Microplastics and Nanoplastics Using In Vitro Model of the Human Intestine—Contribution of Each Cell in the Tri-Culture Models
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Using a lab model of the human intestine, researchers showed that smaller plastic nanoparticles (50 nm) crossed the gut lining more easily than larger ones, with specialized immune-sensing cells playing a key role in uptake. The particles that got through could potentially enter the bloodstream. This study helps explain how the tiniest plastic particles in food and water might get inside the human body.
Uptake and Effects of Micro‐, Submicro‐ and Nanoplastics Investigated on in vitro Models of the Intestinal Barrier and the Liver
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Researchers investigated the uptake and toxic effects of micro-, submicro-, and nanoplastics using in vitro models of the intestinal barrier and liver to assess how plastic particles of different sizes interact with gastrointestinal and hepatic cells. The study examined cellular internalization, barrier integrity, and metabolic responses to characterize size-dependent toxicity mechanisms.
A human Caco-2-based co-culture model of the inflamed intestinal mucosa for particle toxicity studies
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Researchers developed an advanced intestinal co-culture model using human Caco-2 cells to better study the toxicity of particles, including micro- and nanoplastics, on inflamed intestinal tissue. The model incorporates immune cells to simulate intestinal inflammation, providing a more physiologically relevant in vitro system for evaluating how plastic particles interact with the gut barrier under both healthy and inflamed conditions.
Effects of bisphenol A and nanoscale and microscale polystyrene plastic exposure on particle uptake and toxicity in human Caco-2 cells
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Researchers studied how human intestinal Caco-2 cells take up polystyrene plastic particles of five different sizes ranging from 300 nanometers to 6 micrometers. The study found that smaller particles were taken up at higher rates and that co-exposure with bisphenol A increased cellular toxicity, suggesting that nanoscale plastics may pose a greater risk to human intestinal cells than larger microplastics.
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