Dimethylaminoethyl modified curdlan nanoparticles for targeted siRNA delivery to macrophages.

Curdlan, an insoluble and neutral polysaccharide, was produced from Agrobacterium sp. ATCC 31750 and chemically modified with dimethylaminoethyl (DMAE) group to introduce gene binding ability. The resulting DMAE-curdlan was crosslinked with curdlan nanoparticles using epichlorohydrin. The prepared nanoparticles are spherical with an average diameter of 523 ± 195 nm, stable and are highly biocompatible with differentiated THP-1 macrophages with viability of above 90%. They are taken up more efficiently by RAW 264.7 macrophage cells than by L929 fibroblast cells. They increase the expression of M1 macrophage marker genes, TNFα and CXCL10, and decrease the expression of M2 marker, CD206, indicating their ability to activate M1 phenotype and aid in tumor regression. They are also capable of delivering siRNA to human macrophage-like cells efficiently and inhibit ~59% of the expression of target MMP-9 protein. These results indicate that this modified curdlan-based nanoparticle is a promising vehicle for the delivery of siRNAs to macrophages, which could open up treatment strategies for a range of diseases.