RSC advancesSep 29, 2026

Hybrid lipid-based nanogels for delivering mRNA

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 30, 2026

Abstract

Nanolipogels (NLGs) are sub-200 nm carriers that encapsulate green fluorescent protein (GFP) mRNA with efficiencies above 75%.

NLGs are made from a synthetic phospholipid and can be synthesized in a single step, avoiding the complexities of traditional carriers.
The incorporation of reactive headgroups allows for effective loading of mRNA through electrostatic interactions.
NLGs release mRNA in a controlled manner over seven days when exposed to glutathione.
In cell studies, NLGs demonstrated cell viability similar to optimized liposomal controls and significantly outperformed Lipofectamine 2000 in mRNA delivery efficiency.
DMAEMA-based NLGs achieved approximately 10.9-fold higher GFP fluorescence compared to Lipofectamine 2000.

Simplified

Nanoscale drug-delivery systems are central to translating mRNA and other biologic medicines into affordable, scalable products. Existing lipid- and polymer-based carriers are often constrained by costly multi-step syntheses, batch variability and acute immune responses driven by ionisable lipids. Here, we report nanolipogels (NLGs), a hybrid phospholipid-polymer carrier built around a synthetic phospholipid, phosphatidylbutenol, synthesised in a single enzyme-catalysed transphosphatidylation step from 1,2-dioleoyl-sn-glycero-3-phosphocholine. The reactive vinyl-terminated headgroup permits aqueous, one-pot free-radical co-polymerisation with either the permanently charged cationic comonomer 2-(acryloyloxy)ethyl trimethylammonium chloride (AETC) or the pH-responsive comonomer 2-(dimethylamino)ethyl methacrylate (DMAEMA), facilitating the electrostatic loading of mRNA. The resulting NLGs are sub-200 nm in size, encapsulate green fluorescent protein (GFP) mRNA with efficiencies above 75%, and exhibit sustained mRNA release over seven days in the presence of 10 mM glutathione. In HeLa and brain endothelial bEnd.3 cells, NLGs showed cell viability comparable to optimised liposomal controls and substantially higher than that observed with Lipofectamine 2000, while DMAEMA-NLGs produced a ∼10.9-fold increase in GFP fluorescence over Lipofectamine 2000. The combination of benign, scalable chemistry with efficient mRNA delivery positions NLGs as a promising platform for accessible nanomedicine.

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Hybrid lipid-based nanogels for delivering mRNA

Abstract

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