Engineered Design of a Mesoporous Silica Nanoparticle-Based Nanocarrier for Efficient mRNA Delivery in Vivo

We have developed tailor-designed mesoporous silica nanoparticles (MSNPs) specifically for delivering mRNA. Our unique assembly protocol involves premixing mRNA with a cationic polymer and then electrostatically binding it to the MSNP surface. Since the key physicochemical parameters of MSNPs could influence the biological outcome, we also investigated the roles of size, porosity, surface topology, and aspect ratio on the mRNA delivery. These efforts allow us to identify the best-performing carrier, which was able to achieve efficient cellular uptake and intracellular escape while delivering a luciferase mRNA in mice. The optimized carrier remained stable and active for at least 7 days after being stored at 4 degrees C and was able to enable tissue-specific mRNA expression, particularly in the pancreas and mesentery after intraperitoneal injection. The optimized carrier was further manufactured in a larger batch size and found to be equally efficient in delivering mRNA in mice and rats, without any obvious toxicity.

Automated summary

We developed tailor-designed mesoporous silica nanoparticles (MSNPs) for delivering mRNA by electrostatically binding it to the MSNP surface after premixing it with a cationic polymer. We investigated the roles of size, porosity, surface topology, and aspect ratio of MSNPs on mRNA delivery. The optimized carrier achieved efficient cellular uptake and intracellular escape while delivering luciferase mRNA in mice, and enabled tissue-specific mRNA expression without toxicity.