Fig. 6: Inhibition of iRhom1 further promoted the CD44-mediated tumor targeting through reduced CD44 cleavage.
From: Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy
a Cellular uptake of Cy5.5-PCL NPs with or without CS coating in various WT or iRhom1 KO cell lines. n = 3 independent samples. b Transwell assay of transmigration of Cy5.5-PCL NPs with or without CS coating across WT or iRhom1 KO CT26 cells. n = 3 independent samples. c NIRF whole body imaging of WT or iRhom1 KO tumor-bearing mice following i.v. administration of DOX-loaded, Cy5.5-PCL-CP NPs and d the corresponding quantification. n = 7 animals. e Quantitative analysis of biodistribution of DOX in WT or iRhom1 KO tumor-bearing mice (WT). n = 3 independent samples. f CD44 expression levels measured by flow cytometry by staining with an antibody recognizing the CD44 external region. n = 3 independent samples. g Fluorescence images of CD44 external region expression in WT or iRhom1 KO CT26 cells. Bar = 20 μm. h Changes in protein levels of full-length CD44 (CD44-Full) and the cleaved, CD44 membrane-bound fragment (CD44-EXT) in WT or iRhom1 knockout/knockdown cells, with or without ADAM17 inhibitor pretratment. i Changes in protein levels of CD44-Full and the CD44-EXT in WT, iRhom1 knockout and iRhom1 rescue cells, with or without ADAM17 inhibitor treatment. j Cellular uptake of Cy5.5 labeled PCL-CS NPs in WT or iRhom1 knockout/knockdown cells with or without ADAM17 inhibitor pretreatment. n = 3 independent samples. k Cellular uptake of Cy5.5 labeled PCL-CS NPs in WT, iRhom1 knockout/knockdown or iRhom1 rescue cells with or without ADAM17 inhibitor pretreatment. n = 3 independent samples. Data are presented as mean ± s.e.m. in (a, b, d, e, f, j, k). Statistical analysis was performed by one-way ANOVA with Tukey’s post hoc test for comparison in (a, j, k). and two-tailed Student’s t-test for comparison in (b, d, e, f). Data are representative of two independent experiments in (c–e, g–i) and three independent experiments in (a, b, f, j, k). Source data are provided as a Source Data file for (a, b, d, e, f, h, i, j, k).
