Bioreducible Guanidinylated Polyethylenimine for Efficient Gene Delivery

Abstract

Cationic polymers are known to afford efficient gene transfection. However, cytotoxicity remains a problem at the molecular weight for optimal DNA delivery. As such, optimized polymeric gene delivery systems are still a sought-after research goal. A guanidinylated bioreducible branched polyethylenimine (GBPEI-SS) was synthesized by using a disulfide bond to crosslink the guanidinylated BPEI (GBPEI). GBPEI-SS showed sufficient plasmid DNA (pDNA) condensation ability. The physicochemical properties of GBPEI-SS demonstrate that it has the appropriate size (~200 nm) and surface potential (~30 mV) at a nitrogen-to-phosphorus ratio of 10. No significant toxicity was observed, possibly due to bioreducibility and to the guanidine group delocalizing the positive charge of the primary amine in BPEI. Compared with the nonguanidinylated analogue, BPEI-SS, GBPEI-SS showed enhanced transfection efficiency owing to increased cellular uptake and efficient pDNA release by cleavage of disulfide bonds. This system is very efficient for delivering pDNA into cells, thereby achieving high transfection efficiency and low cytotoxicity.

Disulfide‐bond‐containing agamatine‐cystaminebisacrylamide polymer demonstrates better transfection efficiency and lower cytotoxicity than polyethylenimine in NIH/3T3 cells

“…This unique property could be related to the reduction ability of the disulfide bond in the AGM-CBA structure. 40,41 It has been hypothesized that the disulfide bond contained in the structure of AGM-CBA polymer and its reduction response can lead to the degradation of AGM-CBA in the reducible condition of the cytoplasm. With the degradation of disulfide bonds, the original polyplex particles can be dispersed gradually, so that the number of particles containing the reporter gene gets more and pDNA are easier to be released from these dispersed particles.…”

Dual functionalized amino poly(glycerol methacrylate) with guanidine and Schiff-base linked imidazole for enhanced gene transfection and minimized cytotoxicity

“…Herein, the binding potency of polymers and pDNA can be characterized by the decrease of the fluorescence of EB due to the dissociation of the DNA/EB complexes. 38,39 In particular, minimal cytotoxicity of IGEP being above 100% for the entire N/P ratios validated the strategic use of guanidine and imidazole substitution of primary amino groups to obtain the safety profile. As shown in Fig.…”

Synthesis of 1-(P-Vinylphenyl)-2- Diethylaminomethylcyclopropane and Its Radical Copolymerization With Methyl Methacrylate

“…The polymers containing functionally active groups in their composition have a wide range of biomedical activity and are used as bactericides, fungicides, medical products. Most frequently, monomers of vinyl and new monomer series containing carbonyls and amino-groups in the structure are used for preparation of such polymers [1][2][3][4].…”