Comparative study of calf-thymus DNA complexation by low generation PAMAM dendrimers and linear cationic PEGylated block copolymers by time-resolved fluorescence spectroscopy

Abstract

Detailed biophysical knowledge of polyplexes formed by complexation of DNA and a cationic agent is one of the primary requirements for their successful application in vivo. In this present work, time-resolved fluorescence spectroscopy was used to understand the complexation process between i) calf-thymus DNA (ctDNA) and a series of cationic PEGylated block copolymers (BCPs), and ii) ctDNA and commercially available Polyamidoamine (PAMAM) dendrimers of low generations (G1 and G3). Studies revealed that the nature of the polyplexes formed after the DNA compaction process were quite different in the two cases mentioned above, as it depends largely on the nature and structure of the cationic polymers under study. In case of low generation PAMAM dendrimers (G1–G3), the DNA dendriplexes formed were seen to have a relatively less relaxed complex state, as compared to the polyplexes formed between PEGylated cationic BCPs with DNA. In case of cationic BCP37 with the maximum PEG content, the resultant DNA polyplex existed in the most easily relaxed state i.e., DNA was not folded into a fixed conformation but rather existed in several conformations. As the existence of the polyplexed DNA in easily relaxed state eases the release of DNA in presence of biological polyanions in the cells, this kind of a study might be useful for the designing of effective non-viral systems for DNA delivery in near future.