CaClOH-Modified Silica Nanoparticles for mRNA Delivery.

Xian, He; Song, Yaping; Qu, Jingjing; Shi, Yiru; Zhang, Yue; Wu, Weixi; Kim, Minjun; Wang, Yue et al. · Nano Lett · 2025

basic_science · Level V

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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<sub>2</sub> 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<sup>2+</sup> 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 <i>in vitro</i> and <i>in vivo</i>, providing useful delivery tools for mRNA technology development.

Medical subject headings