Improved Cell Viability of Linear Polyethylenimine through γ-Cyclodextrin Inclusion for Effective Gene Delivery
✍ Scribed by Atsushi Yamashita; Hak Soo Choi; Tooru Ooya; Nobuhiko Yui; Hidetaka Akita; Kentaro Kogure; Hideyoshi Harashima
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 247 KB
- Volume
- 7
- Category
- Article
- ISSN
- 1439-4227
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✦ Synopsis
Abstract
A polypseudorotaxane consisting of a linear polyethylenimine with M~n~ of 22 000 (LPEI22k) and γ‐cyclodextrins (γ‐CDs; LPEI22k/γ‐CD) has been examined as a gene carrier. The polyplex formation with luciferase‐encoding plasmid DNA (pDNA), intracellular trafficking of polyplex, cytotoxicity, and transfection efficiency were evaluated by various characteristic methods. LPEI22k/γ‐CD formed a pDNA polyplex at higher N/P ratios than LPEI22k; this suggests that the γ‐CD threading sterically interfered with the polyplex formation. In addition, the ζ potentials of the polyplex significantly decreased due to the reduction in charge density of LPEI22k caused by γ‐CD threading. The cellular uptake of pDNA in the LPEI22k/γ‐CD polyplex was enhanced by free γ‐CDs released from the polyplex that might accelerate the cellular uptake through enhanced membrane affinity. LPEI22k/γ‐CD significantly increased cell viability even at high N/P ratios, and the polyplex showed high transfection efficacy. The low cytotoxicity and high gene expression of LPEI22k/γ‐CD are advantageous to polyplex administration in vivo.