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

• Published in: Nano Letters Vol. 23; no. 6; pp. 2137 - 2147
• Main Authors: Dong, Shuwen, Feng, Zhenhan, Ma, Runpu, Zhang, Tianyu, Jiang, Jinhong, Li, Yibo, Zhang, Yumo, Li, Silu, Liu, Xiao, Liu, Xiangsheng, Meng, Huan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 22.03.2023; American Chemical Society (ACS)
• Subjects: Animals; Mice; Nanoparticles; Porosity; Rats; Silicon Dioxide; tissue-selectivity; mesoporous silica; mRNA; in vivo; nanoparticles
• ISSN: 1530-6984; 1530-6992; 1530-6992
• DOI: 10.1021/acs.nanolett.2c04486

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 °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.