Stability of oligodeoxynucleotide complexes with cationic phospholipid and peptide carriers

The design of efficient cationic lipid and peptide nanocarriers for oligodeoxynucleotide (ODN) delivery into cells requires precise understanding and control of their physical properties. In this work we used X-ray diffraction, fluorescence resonance energy transfer (FRET), dynamic light scattering (DLS) and zeta-potential measurements to characterize the stability of the nanoparticles formed by ODN with cationic phospholipids and with a native cationic peptide, protamine. The most important findings can be summarized as follows: 1) ODNs form stable complexes with protamine and cationic phospholipids at salt concentrations below ~0.5 and ~0.3 M NaCl, respectively. 2) The ODN lipoplexes are typified by tightly packed lamellar phases and disordered ODN arrangement between the lipid bilayers. 3) ODN/protamine complexes with positive zeta-potentials gradually increase in size in the course of hours and days, while the size of nanoparticles with negative zeta-potentials remains constant. 4) There are significant differences between ODN/lipid and ODN/protamine particle size distributions. The former displayed a characteristic maximum at cationic/anionic 1:1 charge ratio, while the latter were not influenced by variations of the ODN/protamine ratio.