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Lipid micelles represent an important class of nanoparticle with the potential to enhance the solubility and delivery of hydrophobic drugs and imaging agents. Their small size (< 50 nm) makes them ideal candidates for both passive tumor uptake and deep tissue penetration. The use of lipid micelles as delivery vehicles, however, 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 (5-16 nucleotides in length). These oligonucleotide-lipid conjugates are synthesized manually using standard phosphoramidite chemistry, and oligonucleotide-stabilized lipid micelles (OLMs) are assembled in aqueous media. Micellar structure can be easily tuned in this approach by modifying lipid structure and oligonucleotide sequence, thus creating a library of OLMs with varying stability. Most importantly, this approach provides a pathway toward the engineering of programmable micelles such that an external trigger leads to monomer exchange with serum proteins and cargo release.
Yanoff, Zenya; Martin, Kailey; Franz, Emily; and Liebenberg, Haley, "Synthesis and Assembly of Oligonucleotide-Stabilized Lipid Micelles" (2020). Biochemistry and Molecular Biology Presentations. 6.
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