CaClOH-Modified Silica Nanoparticles for mRNA Delivery
He Xian, Yaping Song, Jingjing Qu, Yiru Shi, Yue Zhang, Weixi Wu, Minjun Kim, Yue Wang, Chengzhong Yu
Abstract
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 CaCl 2 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 Ca 2+ 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.