Fig. 3: Development and biophysical characterization of POEM nanocarrier for co-delivery of gemcitabine and siSPB9.

a A schematic illustration of PPO/PPOGEM/siRNA (POEM/siRNA) nanocarrier delivery system. b Tissue distribution (H heart, S spleen, Lu lung, Li liver, K kidney, T tumor, T/Li tumor/liver, T/K tumor/kidney, T/Ti tumor/tissues) of POEM/siRNA with different PPO polymers. c Gel-retardation assay of PPO/siRNA complexes at various N/P ratios. d Gel-retardation, size, and zeta potentials (ZP) of POEM/siRNA complexes at various PPO/siRNA N/P ratios and PPOGEM/siRNA mass ratios. n = 3 independent samples. e Size and ZP of PPOGEM/PPO/siRNA (POEM/siRNA) at a ratio of 50/5/1, and Psugar/PPO/siRNA at a ratio of 40/5/1. n = 3 independent samples. f Upper left: Conformational change of POEM/siRNA system before and after MD simulation. Upper right: Radius of Gyration (RoG) of PPOGEM and Psugar during the final 150 ns MD simulation. Bottom: The interaction between siRNA and POEM. siRNA interacts with PPOGEM through both T-shaped π-π interactions (right dash line) and hydrogen bonding (left dash line). g Critical micelle concentration (CMC) of POEM/siRNA and Psugar/PPO/siRNA nanoparticles. h Spherical morphology of POEM/siRNA NPs by cryo-EM. Scale bar, 50 nm. i Cumulative release of gemcitabine at 72 h or 12 h from POEM/siRNA NPs under different conditions. n = 3 independent samples. j Gel-retardation assay of free siRNA or POEM/siRNA after incubation with RNAse. Data are presented as mean  ± s.e.m. in (d, e, i). Statistical analysis was performed by one-way ANOVA with Tukey’s post hoc test for comparison in (i). Source data are provided as a Source Data file.