Bio-reducible polycations from ring-opening polymerization as potential gene delivery vehicles

Abstract

Synthetic polycations show great potential for the construction of ideal non-viral gene delivery systems. Several cationic polymers were synthesized by the epoxide ring-opening polymerization between diepoxide and various polyamines. Disulfide bonds were introduced to afford the polymers bio-reducibility, while the oxygen-rich structure might enhance the serum tolerance and biocompatibility. The polycations have much lower molecular weights than PEI 25 kDa, but still could well bind and condense DNA into nano-sized particles. DNA could be released from the polyplexes by addition of reductive DTT. Compared to PEI, the polycations have less cytotoxicity possibly due to their lower molecular weights and oxygen-rich structure. More significantly, these materials exhibit excellent serum tolerance than PEI, and up to 6 times higher transfection efficiency than PEI could be obtained in the presence of serum. The transfection mediated by was seldom affected even at a high concentration of serum. Much lower protein adsorption of polycations than PEI was proved by bovine serum albumin adsorption experiments. Flow cytometry also demonstrates their good serum resistance ability.

Immune Activities of Polycationic Vectors for Gene Delivery

“…The conventional method used to solve the problem of inherent immunogenicity of polycations is the modification of their structure, in which chemical modification is the most common approach. For example, modifying the two ends or the side chains (Thomas and Klibanov, 2002 ; Arote et al, 2007 ; Yang et al, 2015 ), changing the degree or synthetic methods of polymerization (Kukowska-Latallo et al, 1996 ; Yu et al, 2016 ) and modifying the backbone of polycations by adding cross-linking agents (Wang et al, 2002 ; He et al, 2015 ; Che et al, 2016 ; Song et al, 2016 , 2017 ) have been tried to modify the chemical structure of polycations. Modification of chemical structures has been widely used to lower the toxicity of polycations, and actually it did make some excellent achievements.…”

Aromatic Modification of Low Molecular Weight PEI for Enhanced Gene Delivery

“…Since naked nucleic acids may be easily degraded by nuclease, and the structure of negatively charged phosphates restrict the uptake into cells. Thus, safe and efficient gene delivery vectors are urgently needed [3,4,5,6]. Compared with viral vectors, polycations show lower immunogenicity and a high nucleic acid loading capacity, and they can be easily prepared and their chemical structures may be conveniently modified, exhibiting potential for the construction of ideal non-viral gene delivery systems [7,8,9,10].…”