Systemic administration of single lipid nanoparticle (SLNP)-miR-22-3p inhibits the growth of MDA-MB-231 TNBC xenografts in nude mice
MDA-MB-231 TNBC cells were orthotopically injected into the mammary fat pads of female athymic nude mice. The mice were randomized to two treatment groups: SLNPs incorporating miR-22-3p or SLNP-control miRNA (0.15 mg/kg administered intravenously twice a week for 4 weeks; five mice/group). (A) MDA-MB-231 tumor xenograft volumes were measured weekly and are shown as mean (±SD). The tumor tissues of TNBC xenografts in MDA-MB-231 collected from nude mice that received SLNP-miR-22-3p or control miRNA. (B and C) miR-22-3p (B) and eEF2K mRNA (C) levels were detected by qRT-PCR. ∗p < 0.05 and ∗∗p < 0.01, respectively. (D−G) Protein expressions of p-eEF2 (Thr56) (D), eEF2 (E), and eEF2K (F) were evaluated by western blot. ∗∗∗∗p < 0.0001. (H−J) Immunohistochemistry analysis of Ki-67 proliferation marker (H) and CD31 angiogenesis marker (I) and TUNEL assay showing apoptotic cells (green) were evaluated in in MDA-MB-231 tumors collected from mice treated with SLNP-miR22-3p or SLNP-control miRNA (J). ∗p < 0.05; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001.