Influence of DNA Type on the Physicochemical and Biological Properties of Polyplexes Based on Star Polymers Bearing Different Amino Functionalities

The interactions of two star polymers based on poly (2-(dimethylamino)ethyl methacrylate)with different types of nucleic acids are investigated. The star polymers differ only in theirfunctionality to bear protonable amino or permanently charged quaternary ammonium groups,while DNAs of different molar massed, lengths and topologies are used. The main physicochemicalparameters of the resulting polyplexes are determined. The influence of the polymer' functionalityand length and topology of the DNA on the structure and properties of the polyelectrolyte complexesis established. The quaternized polymer is characterized by a high binding affinity to DNAand formed strongly positively charged, compact and tight polyplexes. The parent, non-quaternizedpolymer exhibit an enhanced buffering capacity and weakened polymer/DNA interactions, particularlyupon the addition of NaCl, resulting in the formation of less compact and tight polyplexes.The cytotoxic evaluation of the systems indicates that they are sparing with respect to the cell linesstudied including osteosarcoma, osteoblast and human adipose-derived mesenchymal stem cellsand exhibit good biocompatibility. Transfection experiments reveal that the non-quaternized polymeris effective at transferring DNA into cells, which is attributed to its high buffering capacity,facilitating the endo-lysosomal escape of the polyplex, the loose structure of the latter one and weakenedpolymer/DNA interactions, benefitting the DNA release.