In order to better evaluate the transport effect of nanoparticles through the nasal mucosa,an in vitro nasal cavity-mimic model was designed based on M cells.The differentiation of M cells was induced by co-culture of...In order to better evaluate the transport effect of nanoparticles through the nasal mucosa,an in vitro nasal cavity-mimic model was designed based on M cells.The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model.The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability.The differentiation of M cells was observed by upregulated expression of Sialyl Lewis A antigen(SLAA)and integrinβ1,and down-regulated activity of alkaline phosphatase.After targeting M cells with iRGD peptide(cRGDKGPDC),the transport of nanoparticles increased.In vivo,the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal administration.In the evaluation of immune effect in vivo,the nasal administration of OVA-PLGA/iRGD led to more release of IgG,IFN-γ,IL-2 and secretory IgA(sIgA)compared with OVA@PLGA group.Collectively,the study constructed in vitro M cell model,and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.展开更多
基金supported by National Natural Science Foundation of China(81603057)Research Funds of Sichuan Science and Technology Department(2019YJ0048 and 19YYJC2250,China)the Fundamental Research Funds for the Central Universities(China),and 111 Project(B18035,China)
文摘In order to better evaluate the transport effect of nanoparticles through the nasal mucosa,an in vitro nasal cavity-mimic model was designed based on M cells.The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model.The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability.The differentiation of M cells was observed by upregulated expression of Sialyl Lewis A antigen(SLAA)and integrinβ1,and down-regulated activity of alkaline phosphatase.After targeting M cells with iRGD peptide(cRGDKGPDC),the transport of nanoparticles increased.In vivo,the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal administration.In the evaluation of immune effect in vivo,the nasal administration of OVA-PLGA/iRGD led to more release of IgG,IFN-γ,IL-2 and secretory IgA(sIgA)compared with OVA@PLGA group.Collectively,the study constructed in vitro M cell model,and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.