CaClOH-Modified Silica Nanoparticles for mRNA Delivery

Messenger RNA (mRNA) technology has attracted wide attention in biomedical applications; its success relies heavily on the development of effective delivery tools. Herein, we report the synthesis of a novel CaClOH-modified silica nanoparticle (SNP-CaClOH) with a spiky surface for mRNA delivery. SNP-CaClOH is obtained by a rationally designed thermal decomposition process of hydrated CaCl₂ inside the silanol-rich mesopores of preformed spiky SNPs. When used as a carrier for the cellular delivery of mRNA, the unique composition of CaClOH offers alkalinity to SNP-CaClOH that promotes endosomal escape via the proton sponge effect. Moreover, SNP-CaClOH leads to an increased intracellular Ca²⁺ level to activate the mammalian target of rapamycin complex 1 (mTORC1) by interacting with calmodulin (CaM) for enhanced mRNA translation. Taking further advantage of the spiky nanotopography, the superior mRNA delivery performance of SNP-CaClOH is demonstrated both in vitro and in vivo, providing useful delivery tools for mRNA technology development.