Synthesis and characterization of polyrotaxanes consisting of cationic alpha-cyclodextrins threaded on poly[(ethylene oxide)-ran-(propylene oxide)] as gene carriers.
Cationic polymers have been receiving growing attention as gene delivery carriers. Herein, a series of novel cationic supramolecular polyrotaxanes with multiple cationic alpha-cyclodextrin (alpha-CD) rings threaded and blocked on a poly[(ethylene oxide)-ran-(propylene oxide)] (P(EO-r-PO)) random copolymer chain were synthesized and investigated for gene delivery. In the cationic polyrotaxanes, approximately 12 cationic alpha-CD rings were threaded on the P(EO-r-PO) copolymer with a molecular weight of 2370 Da and an EO/PO molar ratio of 4:1, while the cationic alpha-CD rings were grafted with linear or branched oligoethylenimine (OEI) of various chain lengths and molecular weights up to 600 Da. The OEI-grafted alpha-CD rings were only located selectively on EO segments of the P(EO-r-PO) chain, while PO segments were free of complexation. This increased the mobility of the cationic alpha-CD rings and the flexibility of the polyrotaxanes, which enhanced the interaction of the cationic alpha-CD rings with DNA and/or the cellular membrane. All cationic polyrotaxanes synthesized in this work could efficiently condense plasmid DNA to form nanoparticles that were suitable for delivery of the gene. Cytotoxicity studies showed that the cationic polyrotaxanes with all linear OEI chains of molecular weights up to 423 Da exhibited much less cytotoxicity than high-molecular-weight branched polyethylenimine (PEI) (25 kDa) in both HEK293 and COS7 cell lines. The cationic polyrotaxanes displayed high gene transfection efficiencies in a variety of cell lines including HEK293, COS7, BHK-21, SKOV-3, and MES-SA. Particularly, the gene delivery capability of the cationic polyrotaxanes in HEK293 cells was much higher than that of high-molecular-weight branched PEI (25 k).
Yang
Chuan
C
Division of Bioengineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore, Republic of Singapore.
Wang
Xin
X
Li
Hongzhe
H
Goh
Suat Hong
SH
Li
Jun
J
D000818:Animals; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D004852:Epoxy Compounds / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D043862:Rotaxanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013053:Spectrophotometry; D047391:alpha-Cyclodextrins / Q000737:chemistry*
D002412:Cations; D004852:Epoxy Compounds; D043862:Rotaxanes; D047391:alpha-Cyclodextrins; D011092:Polyethylene Glycols; D004247:DNA; C009068:propylene oxide; C032613:alpha-cyclodextrin