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Biochemistry & Molecular Biology
Lipid micelles are an ideal candidate to enhance solubility and delivery of hydrophobic drugs and imaging agents, due to their small size. However, use of lipid micelles as delivery vehicles has been challenged by the fact that these particles are inherently unstable in vivo due to concentration dependence and interactions with serum proteins. We have developed a minimalist method to stabilize the formation of micelles using lipid monomers covalently modified with short oligonucleotide sequences (16 nucleotides in length). In this study, we sought to determine the effects of lipid tail length to micellar stability. By varying lipid tails or oligonucleotide sequence, micellar structure can be easily tuned to create a library of micelles with varying stability. Our results show that we have successfully synthesized, and purified DNA-lipid conjugates composed of 16 carbon (C16) or 18 carbon (C18) tails with 1 (monoacyl) or two (diacyl) chains. Fluorescence resonance energy transfer assays indicate that the micelles formed from C18diacyl conjugates were most stable, while micelles formed from C16monoacyl conjugates were least stable.
Wun, Jesse, "Synthesis and Stabilization of Oligonucleotide-Stabilized Lipid Micelles: Optimization of Lipid Functional Group" (2022). Biochemistry and Molecular Biology Honors Papers. 11.