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A post-assembly, reversible crosslinking strategy stabilizes lipid nanoparticles against extracellular stresses while permitting mRNA release following disassembly triggered by the acidic endosomal environment. This strategy enhances endosomal escape and increases in vivo mRNA expression.
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References
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Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 6, 1078–1094 (2021). A review article on the design principles, formulation strategies, biological barriers and clinical translation of LNPs for mRNA delivery.
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Gao, W. et al. Resolving the mRNA encapsulation-release trade-off via compensatory forces in engineered ionizable lipids. Adv. Mater. https://doi.org/10.1002/adma.202512235 (2025). A research article that resolves the trade-off in LNPs between stable mRNA encapsulation and efficient intracellular release through ionizable lipid design.
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Zhang, H. & Barz, M. Investigating the stability of RNA-lipid nanoparticles in biological fluids: unveiling its crucial role for understanding LNP performance. J. Control. Rel. 381, 113559 (2025). A review article that discusses how LNP stability in biological fluids is governed by lipid composition and post-assembly interactions, with direct implications for delivery performance.
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Hald Albertsen, C. et al. The role of lipid components in lipid nanoparticles for vaccines and gene therapy. Adv. Drug Deliv. Rev. 188, 114416 (2022). A review article on the roles of lipid components in determining LNP stability and nucleic acid delivery efficiency.
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This is a summary of: Liu, X. et al. Crosslinking of lipid nanoparticles enhances the delivery efficiency and efficacy of mRNA vaccines. Nat. Chem. Eng. https://doi.org/10.1038/s44286-026-00356-5 (2026).
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Reversible post-assembly crosslinking enhances lipid nanoparticle mRNA delivery. Nat Chem Eng (2026). https://doi.org/10.1038/s44286-026-00371-6
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DOI: https://doi.org/10.1038/s44286-026-00371-6
