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.

Temperature-tuned DNA condensation and gene transfection by PEI-g-(PMEO2MA-b-PHEMA) copolymer-based nonviral vectors

“…In Fig. 1(2), the broad peak at d2.5-2.8 ppm is assigned to the methylene of branched 1200 Da PEI [28]; the characteristic peak of hydroxyl in PHEMA at d4.8 ppm disappears completely, which verifies that PEI was grafted to MH-1 by CDI coupling. The copolymerization ratios of MEO 2 MA and HEMA were determined by the integration of OCH 3 and OH peaks.…”

A guanidinylated bioreducible polymer as a novel gene carrier to the corpus cavernosum of mice with high‐cholesterol diet‐induced erectile dysfunction

“…Recently, our colleague also reported low cytotoxicity of GBP in C2C12 mouse myoblast cells and HEK293 human embryonic kidney cells . Besides the positive role in transfection efficiency, guanidinylation of the primary amine groups is also known to enhance cell viability (Bromberg et al, 2009).…”

Nanostructures and Nanostructured Networks for Smart Drug Delivery

“…DNA and siRNA interact with the amino groups of the copolymer, forming a complex inside the micelle (micelleplex), which protects nucleic acids from the enzymatic degradation [152][153][154][155][156]. Despite the use of pH-responsive micelles is still quite incipient, promising results have been already obtained.…”