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 (&lt;20 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 <i>in vivo</i>. As with all micelles, lipid micelles are generated by the self-assembly of monomers and exist in equilibrium with their monomeric lipid components. Thus, even at concentrations higher than the critical micelle concentration (CMC), when exposed to serum proteins, the equilibrium shifts to the monomeric state, releasing any encapsulated components before these particles can reach their target. 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.

Synthesis and assembly of oligonucleotide-stabilized lipid micelles

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.