Post-polymerization functionalized sulfonium nanogels for gene delivery

Abstract

Gene therapy is widely recognized as a promising method in combating diseases caused by gene abnormalities or deletions. The effects of these deletions and mutations are ameliorated through gene therapy by means of transfection vectors. These delivery vehicles are tasked with protecting the gene and transporting it to the cell nucleus when necessary. Nano-sized hydrogel particles, also known as nanogels, are crosslinked polymeric nanoparticles that are promising materials for such biomedical applications. Whereas most cationic carriers for gene delivery are nitrogen-based, we are interested in utilizing a sulfonium moiety to this end. Diversifying the available gene vectors not only satisfies scientific curiosity, it could also offer improved gene delivery efficiencies. Here we describe the synthesis of glycidyl methacrylate (GMA) nanogels as a platform for subsequent functionalization. Ring-opening reactions with diethyl sulfide were carried out to install permanent cationic sulfonium groups on the nanogels, yielding readily water-soluble nanogels with a zeta potential of ζ = +40 ± 0.5 mV at neutral pH and a mean diameter of D = 29 ± 10 nm as determined by transmission electron microscopy (TEM). The degree of functionalization with sulfonium groups was found to be tunable. These nanogels were subjected to post-synthesis modifications resulting in biocompatible sulfonium nanogels containing a thioglycerol moiety. Polyplexes were formed by successful incubation with plasmid DNA encoding for green fluorescent protein (pCMV-GFP), at various ratios. In a next step, nucleic acid delivery by sulfonium nanogels was probed for various cell lines for the first time, showing poor delivery properties.