Franck, Christoph O.Christoph O.FranckBistrovic Popov, AndreaAndreaBistrovic PopovAhmed, IshtiaqIshtiaqAhmedHewitt, Rachel E.Rachel E.HewittFranslau, LuiseLuiseFranslauTyagi, PuneetPuneetTyagiFruk, LjiljanaLjiljanaFruk2023-12-042023-12-042023https://resolver.sub.uni-goettingen.de/purl?gro-2/139104Efficient and biocompatible catch-and-release gene delivery system has been developed using polymer nanocarriers modified with polyHis and polyArg peptides.The design of nanomaterial-based nucleic acid formulations is one of the biggest endeavours in the search for clinically applicable gene delivery systems. Biopolymers represent a promising subclass of gene carriers due to their physicochemical properties, biodegradability and biocompatibility. By modifying melanin-like polydopamine nanoparticles with poly- l -arginine and poly- l -histidine blends, we obtained a novel catch-and-release gene delivery system for efficient trafficking of pDNA to human cells. A synergistic interplay of nanoparticle-bound poly- l -arginine and poly- l -histidine was observed and evaluated for pDNA binding affinity, cell viability, gene release and transfection. Although the functionalisation with poly- l -arginine was crucial for pDNA binding, the resulting nanocarriers failed to release pDNA intracellularly, resulting in limited protein expression. However, optimal pDNA release was achieved through the co-formulation with poly- l -histidine, essential for pDNA release. This effect enabled the design of gene delivery systems, which were comparable to Lipofectamine in terms of transfection efficacy and the catch-and-release surface modification strategy can be translated to other nanocarriers and surfaces.enhttp://creativecommons.org/licenses/by/3.0/journal_article10.1039/D3NH00269A