Hongyu Ren, Xiaolu Yu, Mengyao Li, Zijin Luo, Yi Lin, Yanan Meng, Qiang Cheng* and Tuo Wei*,
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Nebulized Lipid Nanoparticles Deliver mRNA to the Liver for Treatment of Metabolic Diseases
An optimal administration approach is critical for effective mRNA delivery and treatment. Nebulizer inhalation offers a mild, convenient, and noninvasive strategy with high translational potential but primarily focused on lung delivery. In this study, we found that surface charges influence tissue targeting of mRNA lipid nanoparticle (mRNA-LNP) postnebulization. Charged mRNA-LNPs showed lung tropism, while neutral ones targeted the liver when administered via a microsprayer aerosolizer. Using nebulized liver-targeted LNPs (NebuLi LNPs), we successfully delivered therapeutic mRNAs for the treatment of metabolic diseases. In a Hereditary Tyrosinemia Type 1 model, fumarylacetoacetate hydrolase mRNA was effectively delivered to the liver, which helped to maintain mouse body weight, preserve liver function, and delay liver fibrosis. In a Type 2 diabetes model, dulaglutide mRNA was effectively expressed in the liver and exhibited good hypoglycemic effects. Overall, the NebuLi LNPs delivery platform offers a promising noninvasive strategy for metabolic disease treatment.
期刊介绍：
Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including:
- Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale
- Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies
- Modeling and simulation of synthetic, assembly, and interaction processes
- Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance
- Applications of nanoscale materials in living and environmental systems
Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.
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