Coarse-Grained Simulation of Polycation/DNA-Like Complexes: Role of Neutral Block.

ABSTRACT

Complexes formed by polycations and DNA are of great research interest because of their prospective application in gene therapy. Whereas the applications of multiblock based polycation generally exhibit promising features, a thorough understanding on the effect of neutral block incorporated in polycation is still lacking. By using coarse-grained dynamics simulation with the help of a simple model for solvent mediated interaction, we perform a theoretical study on the physicochemical properties of various polyplexes composed of a single DNA-like polyanion chain and numbers of linear polycationic chains with different modifications. By analyzing various properties, we find the hydrophobic/hydrophilic modifications of linear polycations may bring an improvement on one aspect of the properties as gene carrier but also involve a trade-off with another one. In particular, polycation with a hydrophobic middle block and a hydrophilic tail block display distinct advantages among di- and triblock linear polycations as gene carrier, while careful design of the hydrophobic block should be made to reduce the zeta potential. The simulation results are compared with available experimental data displaying good agreements.