Effects of dendrimer/cyclodextrin conjugates as gene transfer carriers on nitric oxide production from macrophages

Abstract

The development of safe gene transfer carriers with high transfection efficiency, which does not affect the cell function, is a challenging issue. In this study, we examined the effects of α-cyclodextrin (α-CyD)/dendrimer conjugate (α-CDE (G3)) on nitric oxide (NO) production in murine macrophages J774.1 cells stimulated with toll-like receptors (TLR) ligands. NO production from macrophages stimulated with TLR ligands was determined by the Griess method. Transfection efficiency of α-CDE (G3)/plasmid DNA (pDNA) complex was quantified by a luminometer. α-CDE (G3) significantly inhibited NO production from J774.1 cells stimulated with TLR ligands. α-CyD molecules in α-CDE (G3) had no effect on NO production. The inhibitory effect of α-CDE (G3) on NO production might be attributed to the dendrimer (G3). Increasing the degree of substitution (DS) of α-CyD in the α-CDE (G3) molecule was accompanied by a significant decrease in the inhibition of NO production. Furthermore, higher gene transfection efficiency of α-CDE (G3)/pDNA complex was observed upon increasing the DS of α-CyD. α-CDE (G3) with high DS value of α-CyD may be considered as a safe gene transfer carrier that does not adversely affect NO production from macrophages stimulated with TLR ligands.