Pyridinium amphiphiles – simple surfactants, gemini surfactants, lipids, lipophilic polycations can act as efficient synthetic transfection systems with reduced toxicity in vitro and in vivo, as previously shown by our group [1-4]. We recently optimized pyridinium cationic lipids and gemini surfactants through comprehensive tuning of the self-assembling process of these amphiphiles at the level of counterion, hydrophobic chain, added co-lipids, their nature and molar ratio [5,6] and we have establish structure-activity and structure-property relationships across different classes of pyridinium amphiphiles [1-6]. We proved that a synergetic effect can be generated by of blending these second-generation pyridinium cationic gemini surfactants into cationic pyridinium lipid bilayers and we established the impact towards plasmid DNA compaction and delivery process. [7]. In the current study we have generated new pyridinium amphiphiles supported on gold nanoparticles and we assessed their physicochemical parameters in parallel with their transfection efficiency as previously described [1-7]. We established that the synergetic action of pyridinium amphiphiles with different molecular curvatures can be extended to composite systems containing amphiphiles supported on highly curved Au nanoparticles and pyridinium lipids. We correlate the composition of these nanoparticles with the dynamics of the DNA compaction process, and with transfection efficiency and cytotoxicity of resulted nucleic acid complexes. We confirmed the broad validity of the concept of synergetic action of pyridinium amphiphiles with different packing parameters and we expanded it to new composite metal-amphiphile DNA delivery systems with high transfection efficiency and negligible cytotoxicity, useful for therapeutic gene delivery. 1. M.A. Ilies et al., J. Med. Chem., 47, 3744-3754 (2004). 2. M.A. Ilies et al, Arch. Biochem. Biophys., 435, 217-226 (2005). 3. M.A. Ilies et al, J. Med. Chem., 49, 3872-3887 (2006). 4. M. A. Ilies T. V. Sommers, L. C. He, A. Kizewski, V. D. Sharma “Pyridinium Amphiphiles in Gene Delivery - Present and Perspectives” in “Amphiphiles: Molecular Assembly and Applications”, R. Nagarajan Ed., ACS Books, 2011, 23-38. 5. S. Savarala et al. Biomacromolecules, 14, 2750-2764 (2013). 6. V. D. Sharma et al. Biomaterials, 34, 6906-6921 (2013). 7. V. D. Sharma, J. Lees, N. E. Hoffman, E. Brailoiu, M. Muniswamy, S. L. Wunder, and M. A. Ilies, Mol. Pharm., 11 (2), 545–559 (2014)

Synergetic DNA delivery with pyridinium amphiphiles with different packing parameters – toward composite DNA delivery systems

249th National Meeting (2015)

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