Disulfide‐Containing Hyperbranched Polyethylenimine Derivatives via Click Chemistry for Nonviral Gene Delivery

Abstract

Reducible disulfide‐containing hyperbranched PEI‐SS‐HP was synthesized via click chemistry and evaluated as nonviral gene carrier. The structure of the polymers was confirmed by 1H NMR and FTIR. It was shown that the PEI‐SS‐HP was able to bind plasmid DNA to positively charged nanoparticles. The reduction sensitivity of the PEI‐SS‐HP was confirmed by gel retardation assay in the presence of DTT mimicking an intracellular reductive environment. In vitro experiments revealed that the reducible PEI‐SS‐HP not only had much lower cytotoxicity, but also posed superior transfection activity as compared to non‐degradable 25‐kDa PEI. The results indicate that a reducibly degradable PEI‐SS‐HP can be a promising gene vector.

Efficient RNA delivery by integrin-targeted glutathione responsive polyethyleneimine capped gold nanorods

“…3Ad). This result suggests that free RGD peptides can inhibit the uptake of the RGD-modified GNR through competitive binding to the tumor cell over-expressed α v β 3 integrins, leading to greatly reduced cellular uptake by blocking the effective α v β 3 integrins -mediated endocytosis [46,48,49].…”

“…RDG/shRNA complexes at different mass ratios were prepared as described above. After incubation for 30 min, GSH was added directly into the nanoparticle solution to reach a final concentration of 3 mM, which was comparable to the intracellular environment [48]. The nanoparticle solution was incubated at 37 °C for 30 min before agarose gel electrophoresis.…”

Polymeric biomaterials with engineered degradation

“…Many groups have also explored reducible substrates for delivering genetic information to cells. Disulfide linkages linking together smaller poly(ethyleneimine) (PEI) chains have been reported by several groups . In most cases, transfection efficiency is compared to 25 kDa branched PEI, a common vector.…”

“…In most cases, transfection efficiency is compared to 25 kDa branched PEI, a common vector. In a typical example, Jiang et al prepared hyperbranched disulfide‐linked PEI, and used it to form polyplexes with plasmid pcDNA3‐Luc and pEGFP (reporter genes for luciferase and green fluorescent protein, respectively) . Compared to non‐degradable branched PEI (25 kDa), the hyperbranched disulfide linked PEI was significantly less toxic to 293T cells.…”

Bioreducible poly(amido amine)s with different branching degrees as gene delivery vectors

“…Compared to their linear counterparts (Parhamifar et al, 2010), branched cationic polymers have different types of amines, and thus different basicity and degree of protonation, which might influence their interactions with cell membranes and thereby cellular uptake, endosomal escape and transfection processes Jiang et al, 2011). For instance, partially degraded polyamidoamine dendrimers achieved higher transfection efficiency than did intact dendrimers due to the increased flexibility and enhanced buffering capacity in endosomes (Tang et al, 1996).…”