Complex formation between cationic polymethacrylates and oligonucleotides

With regard to the development of pharmaceutical carriers for oligonucleotides, the interactions between a cationic polymer, poly(2-dimethylamino)ethyl methacrylate (pDMAEMA), and rhodamine-labeled 25-mer phosphodiester oligonucleotides (Rh-ONs) were studied. The composition of the pDMAEMA/Rh-ON complexes was investigated as a function of the charge ratio (phi; +/-) by increasing the pDMAEMA concentration and keeping the Rh-ON concentration constant. Gel electrophoresis revealed that at phi < 1 only a fraction of the short Rh-ONs bind the longer pDMAEMA chains. Dynamic light scattering and zeta potential () indicated that at phi < 1 only a fraction of the phosphate anions on the Rh-ONs are involved in complex formation which results in dangling of the Rh-ONs. Moreover, from fluorescence measurements, multimolecular complexes (i.e., several Rh-ONs per pDMAEMA chain) were revealed. At 1 < phi < 3, approximated zero. This led to a clustering of individual complexes. At phi > 3, all the Rh-ONs were bound while, compared to complexes at phi < 1, the average number of Rh-ONs bound to one pDMAEMA chain was decreased. The presence of multimolecular complexes was confirmed from fluorescence correlation spectroscopy (FCS) measurements. The multimolecular complexes were observed as highly intense fluorescent particles upon their diffusion through the confocal volume of the FCS instrument. Also, the decrease in the average number of Rh-ONs bound to one pDMAEMA chain, upon increasing , was confirmed by FCS.