Journal article
The effect of side-chain functionality and hydrophobicity on the gene delivery capabilities of cationic helical polypeptides
Department of Materials Science and Engineering, University of Illinois at Urbana–Champaign, 1304 W Green Street, Urbana, IL, 61801, USA1
The rational design of effective and safe non-viral gene vectors is largely dependent on the understanding of the structure-property relationship. We herein report the design of a new series of cationic, α-helical polypeptides with different side charged groups (amine and guanidine) and hydrophobicity, and mechanistically unraveled the effect of polypeptide structure on the gene delivery capability.
Guanidine-containing polypeptides displayed superior membrane activities to their amine-containing analogues via the pore formation mechanism, and thus possessed notably higher transfection efficiencies. Elongating the hydrophobic side chain also potentiated the membrane activities of the polypeptides, while at the meantime caused higher cytotoxicities.
Upon an optimal balance between membrane activity and cytotoxicity, maximal transfection efficiency was achieved which outperformed commercial reagent Lipofectamine™ 2000 (LPF2000) by 3–6 folds. This study thus provides mechanistic insights into the rational design of non-viral gene delivery vectors, and the best-performing materials identified also serve as a promising addition to the existing systems.
| Language: | Undetermined |
|---|---|
| Year: | 2015 |
| Pages: | 3443-3454 |
| ISSN: | 18785905 and 01429612 |
| Types: | Journal article |
| DOI: | 10.1016/j.biomaterials.2013.12.097 |
Cations Gene Transfer Techniques Guanidine Hydrophobic and Hydrophilic Interactions Hydrophobicity Kinetics Magnetic Resonance Spectroscopy Non-viral gene delivery Peptides Structure–function relationship guanidine hydrophobicity non-viral gene delivery structure-function relationship α-Helical polypeptide α-helical polypeptide
