Furan-rich, biobased transfection agents as potential oligomeric candidates for intracellular plasmid DNA delivery†

Abstract

Biobased, DNA delivery vectors have been synthesized with a core motif composed of 2,5-bishydroxymethylfuran (BHMF) readily available from an important biomass feedstock 5-hydroxymethyl furfural (HMF). To generate the product, BHMF was first converted to 2,5-furan bishydroxymethyl diacrylate (2,5-FDA), which was later conjugated with different types of secondary amines. Rich in tertiary nitrogen, these oligomeric FDA-amino esters demonstrated stable electrostatic interactions with negatively charged plasmid DNA in an aqueous environment. We evaluated synthetic routes toward these plasmid DNA-binding amino esters (pFASTs), identified their nanoscale features, and attempted to establish their structure–property relationship in the context of the DNA delivery. Our preliminary studies show that the pFASTs formed stable complexes with the plasmid DNA. Dynamic light scattering indicated that the DNA polyplexes of pFASTs have hydrodynamic diameters within the size range of 100–150 nm with a surface charge (ζ-potential) ranging from −10 to +33 mV, depending on pFAST type. These oligomeric amino esters rich in furan motif were also found to successfully transfect the GFP-expressing plasmid DNA intracellularly. Collectively, this study establishes a new route to produce DNA transfection agents from sustainable resources that can be used for transferring genetic materials for humans, veterinary, and agrochemical purposes.