Design of multi-functional nanoparticles as a DNA carrier

Abstract

Novel biodegradable nanoparticles which contain the sites for both polynucleotide adsorption and targeting ligand on their surfaces were prepared as a carrier for genetic materials. The nanoparticles were obtained from poly( d, l-lactic acid) and poly( l-lysine)- graft-polysaccharide copolymers by using a diafiltration method. The size of the particles was controlled by varying the initial concentration of the graft copolymer or by changing the polysaccharide content in the graft copolymers. Polysaccharide moieties on the surface of the nanoparticles were found to interact specifically with a corresponding lectin. The number of amino groups on the nanoparticles surfaces increased with increasing polysaccharides content in the graft copolymers, suggesting that grafted polysaccharide chains modify the adsorption conformation of poly(L-lysine) moiety in the graft copolymer on the nanoparticle surface. Both plasmid DNA and oligonucleotide (40 mer) were adsorbed stably on the nanoparticles surfaces through the ionic interaction between polynucleotides and poly(L-lysine) segments without inducing inter-particle aggregation. Our results suggest that the nanoparticles prepared from poly( d, l-lactic acid) and poly( l-lysine)- graft-polysaccharide copolymer basically form a multi-layered structure composed of polysaccharide-rich surface, poly( l-lysine)-rich intermediate, and poly( d, l-lactic acid)-cored inner layers. The nanoparticles offer several advantages such as ease in DNA loading, stable dispersiveness in aqueous media, and polysaccharide-based surface functionality, implying usefulness of the particles as a carrier and/or controlled release matrix of polynucleotides.