CaClOH-Modified Silica Nanoparticles for mRNA Delivery
Date
2025
Authors
Xian, H.
Song, Y.
Qu, J.
Shi, Y.
Zhang, Y.
Wu, W.
Kim, M.
Wang, Y.
Yu, C.
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Journal article
Citation
Nano Letters, 2025; 25(16):6365-6373
Statement of Responsibility
He Xian, Yaping Song, Jingjing Qu, Yiru Shi, Yue Zhang, Weixi Wu, Minjun Kim, Yue Wang, Chengzhong Yu
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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 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.
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© 2025 American Chemical Society.