ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Lung-Specific mRNA Delivery by Ionizable Lipids with Defined Structure-Function Relationship and Unique Protein Corona Feature.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- From RNA design to delivery: Computational strategies for functional RNA therapeutics.Bioactive materials · 2027Review
- Overcoming hepatic tropism: Precision engineering of lipid nanoparticles for extrahepatic RNA delivery.Materials today. Bio · 2026Review
- Ligand-Mediated Reprogramming Redirects Liver-Tropic Ionizable Lipid Nanoparticles for Lung-Selective mRNA Delivery.Angewandte Chemie (International ed. in English) · 2026Article
- Tuning protein corona on nucleic acid nanodrugs for targeted delivery.Acta pharmaceutica Sinica. B · 2026Review
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- From Morphology to Mechanism: Cryo-Electron Microscopy Insights into Lipid Nanoparticles for RNA Delivery.ACS nano · 2026Review
- Optimized Lipid Nanoparticles with Tail-Modified Ionizable Lipids for Safer mRNA Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026Review
- Article
- Endosome-phagophore linking assemblies for the degradation of membrane/extracellular proteins.Nature communications · 2025Article
- Structure-Based Modeling of Environment-Dependent Protonation States Across LNP Formulations with Atomistic CpHMD.Molecular pharmaceutics · 2025Article
- A naturally derived lipopeptide lipid nanoparticle platform enabling multiple nucleic acids delivery.Bioactive materials · 2025Article
- PEGylation Enhances Colloidal Stability and Promotes Ligand-Mediated Targeting of LAF-Xenopeptide mRNA Complexes.Polymers · 2025Article
- Application of nanoparticles in the treatment of acute lung injury: Current situation and future directions.Materials today. Bio · 2025Review
- Targeted delivery ofActa pharmaceutica Sinica. B · 2025Article
- Recent strategies for enhanced delivery of mRNA to the lungs.Nanomedicine (London, England) · 2025Review
- Lung-Specific mRNA Delivery by Ionizable Lipids with Defined Structure-Function Relationship and Unique Protein Corona Feature.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
Targeted delivery of mRNA with lipid nanoparticles (LNPs) holds great potential for treating pulmonary diseases. However, the lack of rational design principles for efficient lung-homing lipids hinders the prevalence of mRNA therapeutics in this organ. Herein, the combinatorial screening with structure-function analysis is applied to rationalize the design strategy for nonpermanently charged lung-targeted ionizable lipids. It is discovered that lipids carrying N-methyl and secondary amine groups in the heads, and three tails originated from epoxyalkanes, exhibiting superior pulmonary selectivity and efficiency. Representative ionizable lipids with systematically variation in chemical structures are selected to study the well-known but still puzzling "protein corona" adsorbed on the surface of LNPs. In addition to the commonly used corona-biomarker vitronectin, other arginine-glycine-aspartic acid (RGD)-rich proteins usually involved in collagen-containing extracellular matrix, such as fibrinogen and fibronectin have also been identified to have a strong correlation with lung tropism. This work provides insight into the rational design of lung-targeting ionizable lipids and reveals a previously unreported potential function of RGD-rich proteins in the protein corona of lung-homing LNPs.
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