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Abstract Orally administered nanocarriers play an important role in improving druggability, promoting intestinal absorption, and enhancing therapeutic applications for the treatment of local and systemic diseases. However, the delivering efficiency and cell response in mucosa to orally administered nanocarriers is affected by the physiological environment and barriers in the gastrointestinal tract, the physicochemical properties of the nanocarriers, and their bidirectional interactions. Goblet cells secrete and form extracellular mucus, which hinders the movement of nanoparticles. Meanwhile, intestinal epithelial cells may absorb the NPs, allowing for their transcytosis or degradation. Conversely, nanoparticle-induced toxicity may occur as a biological response to the nanoparticle exposure. Additionally, immune response and cell functions in secretions such as mucin, peptide, and cytokines may also be altered. In this review, we discuss the bidirectional interactions between nanoparticles and cells focusing on enterocytes and goblet cells, M cells, and immune cells in the mucosa according to the essential role of intestinal epithelial cells and their crosstalk with immune cells. Furthermore, we discuss the recent advances of how the physiochemical properties of nanoparticles influence their interplay, delivery, and fate in intestinal mucosa. Understanding the fate of nanoparticles with different physiochemical properties from the perspective of their interaction with cells in mucosa provides essential support for the development, rational design, potency maximation, and application of advanced oral nanocarrier delivery systems. Graphical Abstract |
