Synthesis and Gene Delivery of Poly(amido amine)s with Different Branched Architecture

Abstract

A general strategy to improve the transfection efficiency as well as lower the cytotoxicity for polycationic vectors has been developed. Through the polycondensation addition of N,N'-methylene bisacrylamide and 1-(2-aminoethyl)piperazine in a water/N,N-dimethylformamide cosolvent, a series of cationic poly(amido amine)s with same repeating units but different branched architecture have been prepared. With the increase in branched architecture, the cationic polymers become more and more compact, accompanied by the enhancement of primary and tertiary amino groups. Therefore, the buffering capacities and DNA condensation capabilities of cationic poly(amido amine)s are strengthened greatly, whereas the correspondent cytotoxicity decreases. Correspondingly, the transfection efficiency is improved by more than three orders of magnitude. The results of this study indicate that the gene delivery can be readily regulated by only changing the branched architecture of polycations.

An efficient nonviral gene-delivery vector based on hyperbranched cationic glycogen derivatives

“…4,16 Each sample solution (0.2 mg/mL) was prepared in 30 mL of an aqueous NaCl solution (0.15 mol/ mL). The sample solutions were initially titrated with a 0.1 mol/mL NaOH solution to a pH of 10.0.…”

“…21 Therefore, the result may indicate that pDNA-binding and -condensation abilities are enhanced with the increase in the fraction of branching units of the hyperbranched polysaccharide derivatives, in agreement with the literature. [4][5][6][7] This is closely related to their genedelivery efficacy, which needs to be investigated in the future.…”

“…[3][4][5][6][7][8] In contrast to linear cationic polymers, hyperbranched cationic polymers exhibit higher levels of gene expression, probably because of the following two factors: 1) they present compact and globular structures in combination with a significant number and variety of different amine groups, which are advantageous for the binding and condensation of DNA into compact particles, resulting in improved protection and endocytosis of DNA; [4][5][6][7] and 2) they exhibit better proton-buffer capacity, which is beneficial for the escape of DNA from endosomes. 4,8 Synthetic hyperbranched cationic polymers, however, such as branched polyethyleneimine (bPEI) and poly(amidoamine) (PAMAM) dendrimers, are still associated with cytotoxicity, biocompatibility, and biodegradability issues, which need to be overcome to allow for in vivo application. 9,10 Natural polysaccharides, due to their outstanding nontoxicity, good biocompatibility and biodegradability, and molecular diversity for chemical modification, have received increasing attention as gene-delivery vectors.…”

Effect of Synthetic Polymers on tRNA Nanoparticle Formation

“…Dendrimers (Scheme 1) are also unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape with strong affinity towards DNA and RNA complexation [4][5][6][7][8][9][10]. It has been shown that synthetic polymers induce significant changes in DNA and RNA solubility and structure under given conditions [8][9][10][11][12][13][14][15][16][17][18][19][20]. Synthetic polymers are also used to transport miRNA and siRNA in vitro [11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”

“…It has been shown that synthetic polymers induce significant changes in DNA and RNA solubility and structure under given conditions [8][9][10][11][12][13][14][15][16][17][18][19][20]. Synthetic polymers are also used to transport miRNA and siRNA in vitro [11][12][13][14][15][16][17][18][19][20][21][22][23][24]. PEGylation of synthetic polymers such as dendrimers is shown to reduce toxicity and increase biocompatibility and DNA Transfection [6,7,9].…”