Precise intracellular uptake and endosomal release of diverse functional mRNA payloads via glutathione-responsive nanogels.

ABSTRACT: We present a novel, highly customizable glutathione-responsive nanogel (NG) platform for efficient mRNA delivery with precise mRNA payload release control. Optimization of various cationic monomers, including newly synthesized cationic polyarginine, polyhistidine, and acrylated guanidine monomers, allowed fine-tuning of NG properties for mRNA binding. By incorporating a poly(ethylene) glycol-based disulphide crosslinker, we achieved glutathione-triggered mRNA release, enabling targeted intracellular delivery. Our NGs demonstrated superior encapsulation (up to 89.3 %) and loading (10.7 %) efficiencies, with controlled mRNA release kinetics at intracellular glutathione concentrations. NGs outperformed commercial transfection reagents across multiple cell lines, including traditionally diffic

SUBMITTER: Dabas R 

PROVIDER: S-EPMC11745970 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature