The development of mass spectrometric analytical methods for the determination of the biological fate of lipid-based drug delivery nanoparticles

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The proposed research program aims at determining the fate of cationic-lipid based nanoparticles within cell tissue cultures, utilizing state-of-the-art mass spectrometric techniques. Cationic lipid nanoparticles have demonstrated a great potential as gene delivery systems. However, it is not fully understood what happens to the delivery system once the gene is delivered to the targeted tissue/cell. My research program can address this essential gap in knowledge. Different cationic lipids have varying toxicological profiles in cell cultures as changes in the chemical structure of the cationic lipids has modified the cell viability profile (i.e. toxicity) upon exposure. In this program, I am evaluating the fate of two structurally related cationic lipid groups, namely diquaternary ammonium gemini surfactants (that include 2 different structural subfamilies) and novel gemini pyridinium surfactants. These compounds are chosen because they have shown promise as gene delivery systems and exhibit different toxic profiles within cultured cells. Variation in toxicity, based on chemical modifications, was also observed within each group. The proposed research will monitor the fate of the tested cationic lipids including subcellular localization and metabolite formation. Their behavior within cells may explain the variation in the toxic profiles among different cationic lipids. The long term goal of my research program is to enhance our understanding of the interactions between the chemical structure of cationic lipids and biological systems (i.e. tissue cultures). The knowledge produced will be used in engineering new lipid materials that are non-toxic and efficient in gene delivery.