Self-assemblies of enzymatically degradable amphiphilic oligopeptides as nonviral gene carrier |
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| Authors: | Tomoko Hashimoto Reiko Iwase Akira Murakami Tetsuji Yamaoka |
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| Institution: | aDepartment of Biomedical Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan;bDepartment of Biomolecular Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan;cDepartment of Biosciences, Teikyo University of Science and Technology, 2525 Yatsusawa, Uenohara, Yamanashi 409-0193, Japan |
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| Abstract: | Novel biodegradable oligopeptide-type gene carriers composed of cationic residues (KRRRKRKRRRKRKRRC) and oligo leucine segments were developed. The amphiphilic carrier was found to form micelle-like assemblies in aqueous solutions, when the oligo leucine is 12 amino acids length (Pep-L12). NMR, CMC, and GPC analysis revealed their hydrophobic/cationic core/shell morphology. Hydrophobic interaction between leucines is thought to be the major driving force behind formations of assemblies. The transient expression of luciferase introduced to COS-1 cells using Pep-L12 below the CMC is as low as that by the control cationic peptides without leucine residue (Pep-L0), while improved transgene expression was observed in the case of Pep-L12 above CMC. The self-assembly raised the apparent molecular weight and gene transfection ability without loosening their low cytotoxicity. These results indicate that the amphiphilic oligopeptides are very promising materials as highly efficient and less toxic gene carriers. |
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| Keywords: | Polymeric gene carrier Self-assembly Stability Oligopeptide Molecular weight |
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