Engineering morphology of tetrasulfide-incorporated mesoporous silica nanoparticles for enhanced mRNA delivery

Lipid nanoparticles, currently the most studied carriers for mRNA delivery, face limitations such as limited cellular uptake, low efficacy, and poor stability. This study introduces a novel tetrasulfide-incorporated virus-like porous silica (VLPSi) nanoparticle as a safer and more efficient alternative for enhancing LNP-mediated mRNA delivery.

By adjusting synthesis parameters, researchers created nanoparticles with diverse morphologies and architectures, allowing them to investigate how tetrasulfide and particle shape impact mRNA delivery.

To maximize VLPSi's performance, scientists evaluated cellular uptake, cytotoxicity, and transfection efficiency using various lipid and mRNA compositions across multiple cell types. The findings revealed that elongating the length and increasing the number of spikes on the VLPSi surface substantially improved cellular uptake efficiency and subsequent mRNA expression.

Mechanistically, this enhanced delivery was attributed to the combined effects of nanospikes and intracellular tetrasulfide degradation. Moreover, the nanoparticles significantly boosted mRNA stability.

These results establish a clear relationship between virus-like topography, biodegradable silica chemistry, and mRNA delivery. This bioinspired nanoplatform offers structural tuning, biodegradability, and high effectiveness, offering a promising approach to improve mRNA delivery.