Block Copolymer Self-Assembly into Monodispersive Nanoparticles with Hybrid Core of Antisense DNA and Calcium Phosphate

Abstract

Self-assembled particles comprised of calcium phosphate, oligonucleotide, and block copolymers of poly(ethylene glycol)-block-poly(aspartic acid) (PEG-PAA) were prepared by the simple mixing of calcium/DNA and phosphate/PEG-PAA solutions. It was shown that the block copolymerization of PEG and PAA segments is essential to prevent precipitation of calcium phosphate crystals and to allow nanoparticles to form. With dynamic light scattering measurements, the diameters of the particles were determined to be around 100 nm with a significantly narrow size distribution. The particles have the ability to incorporate DNA in the core with sufficient efficiency as determined by gel permeation chromatography and fluorescence measurements. Further, the cytotoxicity of the particles assessed by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay was significantly low. The organic−inorganic hybrid nanoparticles containing DNA molecules thus prepared are expected to be utilized as DNA delivery systems for gene and antisense therapy.