Polystyrene nanoparticles were prepared by surfactant-free emulsion polymerization using water-soluble cationic initiators to induce a positive surface charge. Reaction conditions were optimized to obtain monodisperse polymeric particles with mean diameters of 150-200 nm. The nanospheres were characterized by scanning electron microscopy, photocorrelation spectroscopy, conductometric titrations, zeta potential measurements, and investigations of their colloidal stability in different media. Sterically stabilized polymeric latexes, showing a low cytotoxicity in the concentrations required for antisense experiments, are capable of binding negatively charged oligonucleotides. The influence of pH, type of latex, and oligonucleotide modification on the adsorption characteristics was investigated. The results indicate that high attractive forces in terms of multiple electrostatic interactions are predominantly responsible for oligonucleotide binding. Comparing the experimental data with calculations based on the random sequential adsorption (RSA) model, it appears that the surface coverage at the saturation level can be considered as a monolayer of "side-on" adsorbed molecules. Oligonucleotide release can be induced by the addition of anionic surfactants or by increasing the pH of the dispersion medium. Investigations of the enzymatic degradation by micellar electrokinetic capillary chromatography (MECC) indicate a significantly enhanced stability of adsorbed oligonucleotides against nuclease attack.