Cationic Polyamidoamine Dendrimers as Modulators of EGFR Signaling In Vitro and In Vivo.

摘要: Cationic polyamidoamine (PAMAM) dendrimers are branch-like spherical polymers being investigated for a variety of applications in nanomedicine including nucleic acid drug delivery. Emerging evidence suggests they exhibit intrinsic biological and toxicological effects but little is known their interactions with signal transduction pathways. We previously showed that the activated (fragmented) generation (G) 6 PAMAM dendrimer, Superfect (SF), stimulated epidermal growth factor receptor (EGFR) tyrosine kinase signaling—an important signaling cascade regulates cell growth, survival apoptosis- cultured human embryonic kidney (HEK 293) cells. Here, we firstly studied vitro Polyfect (PF), non-activated (intact) G6 on EGFR via extracellular-regulated 1/2 (ERK1/2) p38 mitogen-activated protein (MAPK) HEK 293 cells then compared vivo single administration (10mg/kg i.p) PF or SF kidneys normal diabetic male Wistar rats. exhibited dose- time-dependent inhibition EGFR, ERK1/2 MAPK phosphorylation HEK-293 similar to AG1478, selective inhibitor. Administration non-diabetic animals 24h inhibited whereas both sets animals. PF-mediated as well apoptosis could be significantly reversed by co-treatment antioxidants such tempol implying these involved an oxidative stress-dependent mechanism. These results show first time can differentially modulate pathway may represent novel class modulators. findings have clinical implications use nanomedicine.