Biophysical Characterizations and Applications of DNA-Lipid Micelles

DNA–lipid conjugates are amphiphilic molecules where a lipid is covalently attached to DNA, enabling applications that leverage both DNA programmability and lipid micelle self-assembly. This work describes two independent but conceptually linked projects using DNA–lipid conjugates for drug delivery and chemical synthesis. In the first project, DNA–lipid conjugate micelles are explored for drug delivery to resolve the instability of lipid micelles upon dilution or interaction with serum proteins like albumin. DNA–lipid conjugates synthesized by solid-phase chemistry self-assemble into micelles whose stability is enhanced through DNA-DNA interactions, such as G-quadruplex or duplex formation. The second project explores DNA–lipid conjugates as catalysts for enantioselective organic synthesis, where the lipid promotes reagent– DNA interactions and the DNA serve as a chiral scaffold for a metal catalyst. Complexation of a copper–bipyridyl catalyst with the DNA scaffold and successful catalysis of a Michael addition demonstrate the feasibility of this micellar DNA-based catalytic system as a potential alternative to traditional organic solvent-dependent synthesis.