Fig. 3: Neural differentiation of MSCs directed by APOs@^atRANBP_miR-124.

a The morphology and size distribution of APOs@^atRANBP_miR-124. b B 1 s spectra of APOs@^atRANBP_miR-124 and physical mixture of APOs, atRAN, and BP_miR-124 measured by XPS. c In vitro release behavior of atRAN from APOs@^atRANBP_miR-124 at different conditions. The media conditions of pH 7.4 and 5.0 simulated culture medium and lysosomes of MSCs, respectively, while the medium of pH 5.0 or pH 7.4 in the presence of 0.1 mM H₂O₂ simulated ROS-rich lysosomes and cytoplasm after MSC transplantation into AD lesion sites, respectively. 0.1 mM of H₂O₂ pre-treatment at pH 5.0 for 6 h simulated ROS-rich cytoplasm post-escape from lysosomes. d In vitro release behavior of miR-124 from APOs@^atRANBP_miR-124 at different media conditions as described above. e Immunofluorescence analysis of eMSCs in different groups. MAP2 (green) immunostaining for neurons. GFAP (red) immunostaining for astrocytes. The white arrows indicate positive cells. f Quantification of the proportions of GFAP-positive and MAP2-positive cells. g Western blot assay of the expression of GFAP and MAP2 in eMSCs. h Quantification of data from (g). i Morphology of eMSCs (labeled with calcein-AM, green) in different groups. j Mean lengths of neurites in eMSCs of different groups. k Ca²⁺ images of Fluo-4 AM-labeled PBS-MSCs (green) and APOs@^atRANBP_miR-124-eMSCs (green) after addition of physiological buffers containing 50 mM KCl, respectively. The white dashed box indicates the magnified region, and white arrows indicate changes in cell fluorescence. The green hollow circles indicate cell fluorescence intensity. l Representative voltage-dependent membrane currents of PBS-MSCs and APOs@^atRANBP_miR-124-eMSCs. The black dashed box indicates the magnified region. Data were presented as mean ± SD (n = 3 independent samples in c, d, h; n = 10 independent cell samples in j). One-way ANOVA with Dunnett’s multiple comparisons test was used for statistical analysis of h, j. Three independent experiments were performed with similar results and representative results are shown. Source data are provided as a Source Data file.