Novel vectors for gene delivery formed by self-assembly of DNA with poly(L-lysine) grafted with hydrophilic polymers.
Complexes formed between DNA and cationic polymers are attracting increasing attention as novel synthetic vectors for delivery of genes. We are trying to improve biological properties of such complexes by oriented self-assembly of DNA with cationic-hydrophilic block copolymers, designed to enshroud the complex within a protective hydrophilic polymer corona. Poly(L-lysine) (pLL) grafted with range of hydrophilic polymer blocks, including poly(ethylene glycol) (pEG), dextran and poly[N-(2-hydroxypropyl)methacrylamide] (pHPMA), shows efficient binding to DNA and mediates particle self-assembly and inhibition of ethidium bromide/DNA fluorescence. The complexes formed are discrete and typically about 100 nm diameter, viewed by atomic force microscopy. Surface charges are slightly shielded by the presence of the hydrophilic polymer, and complexes generally show decreased cytotoxicity compared with simple pLL/DNA complexes. pEG-containing complexes show increased transfection activity against cells in vitro. Complexes formed with all polymer conjugates showed greater aqueous solubility than simple pLL/DNA complexes, particularly at charge neutrality. These materials appear to have the ability to regulate the physicochemical and biological properties of polycation/DNA complexes, and should find important applications in packaging of nucleic acids for specific biological applications.
Toncheva
V
V
Biomaterials and Polymers Research Group, University of Gent, Gent B9000, Belgium.
Wolfert
M A
MA
Dash
P R
PR
Oupicky
D
D
Ulbrich
K
K
Seymour
L W
LW
Schacht
E H
EH
D000595:Amino Acid Sequence; D000818:Animals; D001704:Biopolymers / Q000378:metabolism / Q000633:toxicity; D002417:Cattle; D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D005333:Fetus; D018390:Gene Targeting / Q000379:methods*; D005813:Genes, Synthetic; D005822:Genetic Vectors / Q000138:chemical synthesis* / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007668:Kidney; D008113:Liver Neoplasms; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010316:Particle Size; D011107:Polylysine / Q000031:analogs & derivatives / Q000235:genetics* / Q000378:metabolism*; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013499:Surface Properties; D014162:Transfection / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014867:Water / Q000378:metabolism
D001704:Biopolymers; D014867:Water; D011107:Polylysine; D004247:DNA