Lipid nanoparticles for nucleic acid delivery to osteoblasts and osteoblast-lineage cells: A systematic review

Background: Lipid nanoparticle (LNP) delivery of nucleic acids is a promising therapeutic platform for addressing bone disorders. A review of LNP formulations that have been studied for nucleic acid delivery to osteoblasts and osteoblast-lineage cells may help guide development of LNPs that are optimized for nucleic acid treatment of bone disorders. Methods: In October 2025, a search of PubMed, Embase, and Web of Science was conducted to systematically review studies on LNPs that have been evaluated for nucleic acid delivery to osteoblasts and osteoblast-lineage cells. Nine studies were included for analysis. Results: In the nine included studies, 11 LNPs were evaluated for nucleic acid delivery to osteoblasts or osteoblast-lineage cells. The LNPs were formulated with various ionizable/cationic lipids, helper lipids, PEGylated lipids, and bone-targeting ligands. They carried mRNA, siRNA, or long non-coding RNA cargos. All LNPs were capable of transfecting target cells with nucleic acids in vitro and/or delivering nucleic acids to bone tissues in rodent models. The delivery efficiency differed between LNPs with different formulations. Cytotoxicity of ionizable LNPs in cell cultures was minimal, and in vivo adverse effects were limited to elevated inflammatory markers for certain LNP formulations. Conclusions: This study catalogs 11 different LNP formulations that are effective for delivery of nucleic acids to bone cells in in vitro and/or in vivo models. Differences in performance and formulation of these LNPs can help inform optimization of LNP formulation for nucleic acid treatment of bone disorders.