Xian, H.Song, Y.Qu, J.Shi, Y.Zhang, Y.Wu, W.Kim, M.Wang, Y.Yu, C.2025-10-162025-10-162025Nano Letters, 2025; 25(16):6365-63731530-69841530-6992https://hdl.handle.net/2440/147813Messenger 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.en© 2025 American Chemical Society.mRNA delivery; CaClOH; silica nanoparticles; endosomal escape; mRNA translationJournal article10.1021/acs.nanolett.4c05615747283Shi, Y. [0000-0001-9734-6574]