Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes.
Cationic polyrotaxanes, obtained by temperature activated threading of cationic cyclodextrin derivatives onto water-soluble cationic polymers (ionenes), form metastable nanometric polyplexes with pDNA and combinations of siRNA with pDNA. Because of their low toxicity, the polyrotaxane polyplexes constitute a very interesting system for the transfection of polynucleotides into mammalian cells. The complexation of Cy3-labeled siRNA within the polyplexes was demonstrated by fluorescence correlation spectroscopy. The uptake of the polyplexes (red) was imaged by confocal fluorescence microscopy using the A549 cell line as a model (blue: nuclei, green: membranes). The results prove the potential of polyrotaxanes for further investigations involving knocking down genes of therapeutic interest.
Department of Drug Delivery, Helmholtz-Institute for Pharmaceutical Research Saarland, Helmholtz-Center for Infection Research (HZI), Saarland University, D-66123 Saarbrücken, Germany.
Prajakta
P
Dandekar
Ratnesh
R
Jain
Manuel
M
Keil
Brigitta
B
Loretz
Leon
L
Muijs
Marc
M
Schneider
Dagmar
D
Auerbach
Gregor
G
Jung
Claus-Michael
CM
Lehr
Gerhard
G
Wenz
D002412:Cations; D002460:Cell Line; D003505:Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004705:Endocytosis; D020868:Gene Silencing; D006801:Humans; D008156:Luciferases / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011119:Polynucleotides / Q000008:administration & dosage* / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D043862:Rotaxanes / Q000138:chemical synthesis / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
D002412:Cations; D003505:Cyclodextrins; D004337:Drug Carriers; D011119:Polynucleotides; D034741:RNA, Small Interfering; D043862:Rotaxanes; D004247:DNA; D008156:Luciferases