Polymeric micelles are attractive delivery vehicles for drug and nucleic acid delivery. We generated a small library of 27 novel lipopolymers by N-acylation of aminoglycoside-derived polymers with aliphatic lipids. Characterization of the lipopolymers based on pyrene fluorescence spectroscopy, dynamic light scattering, and atomic force microscopy (AFM) indicated the formation of 25-50 nm micelles that were stable for several months in aqueous media. The cationic charge on the aminoglycoside-derived micelles was employed for complexation with plasmid DNA, and micelle-DNA complex formation was verified using size and zeta potential measurements. Parallel screening of lipopolymer micelle transgene expression, using luciferase and green fluorescent proteins, indicated efficacies higher than the polymer standard, poly(ethylene imine), in several cancer cell lines. Importantly, transgene expression efficacies were relatively unaffected by presence of serum. In addition to transgene expression, effective lipopolymers were also investigated for gene silencing using shRNA-expressing plasmids (shRNA plasmids) in cancer cells constitutively expressing luciferase protein. Our results indicate that aminoglycoside-derived lipopolymer micelles are attractive vectors for non-viral transgene expression and gene silencing. 

Aminoglycoside-derived lipopolymer micelles for transgene delivery

247th National Meeting (2014)

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