Issue 4, 2024

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.

Graphical abstract: Post-polymerization functionalized sulfonium nanogels for gene delivery

Supplementary files

Article information

Article type
Paper
Submitted
12 Jan 2024
Accepted
26 Mar 2024
First published
15 Apr 2024
This article is Open Access
Creative Commons BY license

RSC Appl. Polym., 2024,2, 678-691

Post-polymerization functionalized sulfonium nanogels for gene delivery

D. N. M. Kusmus, T. van Veldhuisen, S. Michel-Souzy, J. J. L. M. Cornelissen and J. M. J. Paulusse, RSC Appl. Polym., 2024, 2, 678 DOI: 10.1039/D4LP00011K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements