Fig. 6: Therapeutic efficacy of DEX-laden/Lipo-SM-Chol in lipopolysaccharide (LPS)-induced lung inflammation model (a-f), and improved gene delivery efficiency of siRNA-encased LNP--SM-Chol in silencing the multi-drug resistant P-gp gene in colorectal cancer (CRC) tumor model (g-k).

a a table showing the physicochemical characterizations of diverse DEX-laden Lipo with eq. 30 mol % Chol (eq. 64.4 mol % Chol for DEX/Lipo-PChcPC) and 5 mol % DSPE-PEG_2K (n = 3 independent experiments). b the lung inflammation model was established by inoculating LPS (30 μL, 400 μg/mL) into the trachea of mice^10,74; 6 h later, mice (n = 5 mice) were intravenously administered with one dose of free DEX or various DEX/Lipo at 1 mg DEX/kg. 12 h after treatment, 5 independent lung tissues were collected for pro-inflammatory cytokines: interleukin-6 (IL-6) (c), tumor necrosis factor-α (TNF-α) (d) and interleukin-1β (IL-1β) (e) examination^10,85. Representative hematoxylin and eosin staining images from 5 independent lung tissues in each group (f). Scar bar = 100 µm, (n = 5 independent experiments, similar results were observed). g Serum stability analysis of free siRNA or siRNA/LNP (mixed with PBS, v/v = 1:1, incubated at 37 °C) by gel retardation assay with 1% agarose gel electrophoresis⁸⁶, (n = 3 independent experiments, similar results were observed). h CT26 CRC tumor model (n = 3 mice) was established by s.c. injection of 1 × 10⁵ cells to mice. On day 10, when tumors reached ~100 mm³, mice were intravenously injected by different siRNA/LNP formulations (at eq. 39 mol % Chol and 1.5 mol % PEG_2K-C-DMG) at 200 µg P-gp siRNA/kg on day 10, 12 and 14. On day 15, tumors were collected for P-gp mRNA analysis by qRT-PCR. i–k in another parallel efficacy study, mice-bearing CT26 tumors (n = 5 mice; tumors: ~100 mm³) received three i.v. injections (on day 10, 12, and 14) of IRI/Lipo-SM-CSS-Chol or its combination with siRNA/LNP-DMA/SM-CSS-Chol. i, individual tumor growth curves. j, average tumor growth curves. k, on day 15, tumors were isolated for HPLC analysis to measure the IRI intratumoral uptake levels. Data in a (right portion), c–e, h, j, k are expressed as mean ± s.d. Statistical significance was determined by one-way ANOVA followed by Tukey’s multiple comparison test for c–e, h, k or two-tailed, unpaired Student’s t-test for j. Source data are provided as a Source Data file.