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Ritt, Nicolas; Berger, Simone; Wagner, Ernst; Zentel, Rudolf (2020): Versatile, Multifunctional Block Copolymers for the Self-Assembly of Well-Defined, Nontoxic pDNA Polyplexes. In: ACS Applied Polymer Materials, Vol. 2, No. 12: pp. 5469-5481
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In the field of systemically applied, nucleic acid-based drugs, polyplexes are interesting candidates for therapeutic systems. In this study, we synthesized a multifunctional triblock copolymer via reversible addition-fragmentation chain transfer (RAFT) block copolymerization. Due to three orthogonal reactive functionalities (an azide end group, a reactive disulfide block (P(PDSM)), and a reactive ester block (P(PFPMA))), the synthesized polymer system is highly adaptable and can be modified in a tailor-made fashion. After modification with N,N-dimethyl ethylendiamine (DMEDA), the synthesized cationic triblock copolymers form polyplexes with pDNA, even at low N/P ratios. The polyplexes can be stabilized further by cross-linking, having a size range of 113-151 nm in 10 mM NaCl, with high uniformity and low size distribution. measurements indicate a good shielding of the charged polyplex core. Additionally, no significant cytotoxicity of the polyplexes is found. First transfection experiments are positive, but the gene transfer efficiency needs to be improved further. Because of its high modifiability, the presented triblock copolymer system is a good candidate for an adjustable pDNA transport system.