title: Guanidinylated polyethyleneimine-polyoxypropylene-polyoxyethylene conjugates as gene transfection agents.
abstract: Conjugates of linear and branched polyethyleneimine (PEI) and monoamine polyether Jeffamine M-2070 (PO/EO mol ratio 10/31, 2000 Da) were synthesized through polyether activation by cyanuric chloride followed by attachment to PEI and guanidinylation by 1H-pyrazole-carboxamidine hydrochloride. The resulting guanidinylated PEI-polyether conjugates (termed gPEI-Jeffamine) efficiently complexed plasmid DNA, and their polyplexes possessed enhanced colloidal stability in the presence of serum proteins. In vitro studies with mammalian CHO-1, 3T3, and Cos-7 cell lines demonstrated improved transfection efficiency of the pCMVbeta-gal plasmid/gPEI-Jeffamine polyplexes. The guanidinylation of the amino groups of PEI and the conjugation of PEI with the Jeffamine polyether enhanced the conjugates' interaction with genetic material and reduced the cytotoxicity of the polyplexes in experiments with the L929 cell line.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Lev
authors.initials: L
authors.lastname: Bromberg
authors.forename: Svetlana
authors.initials: S
authors.lastname: Raduyk
authors.forename: T Alan
authors.initials: TA
authors.lastname: Hatton
authors.forename: Angel
authors.initials: A
authors.lastname: Concheiro
authors.forename: Cosme
authors.initials: C
authors.lastname: Rodriguez-Valencia
authors.forename: Maite
authors.initials: M
authors.lastname: Silva
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Lorenzo
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004996:Ethidium / Q000737:chemistry; D019791:Guanidine; D006801:Humans; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D011409:Propylene Glycols / Q000737:chemistry; D013816:Thermodynamics; D014162:Transfection / Q000379:methods*; D014867:Water / Q000737:chemistry
chemical_list: D001798:Blood Proteins; D011108:Polymers; D011409:Propylene Glycols; D014867:Water; C012504:polypropylene glycol; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; D004996:Ethidium; D019791:Guanidine