ArticleMaterials today. Bio2025
Precise intracellular uptake and endosomal release of diverse functional mRNA payloads via glutathione-responsive nanogels.
Article in Materials today. Bio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Hybrid lipid-nanogels: nanolipogels for mRNA delivery.RSC advances · 2026Article
- Redox-responsive peptide folding enables intracellular self-assembly and controlled nucleic acid release.Materials today. Bio · 2026Article
- A worm-like nucleic acid nanostructure for gene delivery and endosomal escape via ClC3 ion exchanger.Science advances · 2026Article
- Recent advances in polymer-based drug delivery systems for atopic dermatitis: enhancing therapeutic efficacy and outcomes.Materials today. Bio · 2025Review
- Targeted Delivery of miR-34a via Anti-CD47 Antibody Conjugates for Enhanced Cancer Immunotherapy in Triple Negative Breast Cancer.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
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 difficult-to-transfect lines. We demonstrate the platform's versatility by successfully delivering GFP mRNA, Mango II RNA aptamers, and functionally relevant β2-AMPK mRNA. Furthermore, we used TIRF microscopy to measure exact RNA copy number within the NGs. Notably, mechanistic cellular uptake studies revealed that disulphide-containing NGs exhibit enhanced cellular uptake and endosomal escape, potentially due to interactions with cell surface thiols. This work represents a highly tuneable, efficient, and biocompatible platform for mRNA delivery with relevance for gene therapy and vaccine development.
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Registered trials
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