Fig 2: The intervention of ANRIL/miR-181b-5p/S1PR1 expression in UC mice (A) qRT-PCR of ANRIL expression; (B) qRT-PCR of miR-181b-5p expression; (C) qRT-PCR of S1PR1 mRNA expression; (D) Western blot of S1PR1 protein expression; (E) immunofluorescence of S1PR1 expression, scale bar = 50 µm. **P < 0.01, ***P < 0.001 vs. control; #P < 0.05, ###P < 0.001 vs. model. Data was analyzed using t test or one-way analysis of variance (ANOVA) followed by Tukey’s test.

Fig 3: The regulatory effects of ANRIL/miR-181b-5p on T cell activation in vitro (A) qRT-PCR of ANRIL expression; (B) qRT-PCR of miR-181b-5p expression; (C) CCK-8 assay of cell viability; (D) ELISA of inflammatory parameters (IFN-?, IL-2, IL-10, and TNF-a); (E) DLR assay of the target relationship between miR-181b-5p and S1PR1; (F) qRT-PCR of ANRIL expression. **P < 0.01, ***P < 0.001 vs. control (A–D,F) or mimic NC (E); ##P < 0.01, ###P < 0.001 vs. activation. Data was analyzed using t test or one-way analysis of variance (ANOVA) followed by Tukey’s test.

Fig 4: S1pr expression in the enteric nervous system. (A) RT-PCR was used to determine mRNA expression of S1P receptors in a murine enteric neuronal cell line (EN). As positive controls, the lung (L) was used for S1pr1 and S1pr3, the spleen (S) for S1pr4, and the brain (B) for S1pr5 and Tubb3, which served as a marker control for neuronal origin genes. (B) Expression of S1P receptors was determined in a rat enteric glial cell line (EG). Gfap was used as a control marker gene. (C) RT-PCR results were verified by qRT-PCR in EN and rat EG cell lines. Fold change expression was compared with the marker gene expression of Tubb3 and Gfap. (D) Murine ENS primary cell cultures were stained for S1PR1, S1PR3 or S1PR5 in combination with the corresponding cell type markers GFAP or ßIII-tubulin. Scale bars represent 100 µm. S1PR = sphingosine-1-phosphate receptor. EN = enteric neurons, L = lung, S = spleen, B = brain, EG = enteric glial cells, GFAP = glial fibrillary acidic protein, RT-PCR = reverse transcription polymerase chain reaction, qRT-PCR = quantitative real-time polymerase chain reaction.

Fig 5: a) Photoacoustic (PA) imaging of tumors from orthotopic GL261 tumor‐bearing mice collected before and after tail vein injection of CS‐J NPs or CS‐J@CM/6 NPs (dose: 5 mg kg−1) at different time points (tumors are highlighted by the red dashed circles). b) Imaging of tumor slices stained with rubeanic acid (RA) from GL261 tumor‐bearing mice administered with CS‐J NPs or CS‐J@CM/6 NPs (scale bar: 50 µm). c,d) Detection of GRK2 expression and S1PR1 expression on the CD3+ T cells in the BM of mice from different groups (n = 3). e,f) Flow cytometry analysis of TIM‐3+CD8+ T cells and their percentage in tumor from different group of mice (n = 5). g) Immunofluorescence images of PD‐L1 expression in tumor slices (scale bar: 25 µm). h) Schematic illustration of the specific interaction between ALCAM expressed on the endothelial cells of BBB and CD6 on the CS‐J@CM/6 NPs to make nanoparticles cross the BBB and target tumor.