Lung-Specific mRNA Delivery Enabled by Sulfonium Lipid Nanoparticles

IF 9.6 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
David O. Popoola, Zhi Cao, Yuqin Men, Xinyuan Li, Mariano Viapiano, Stephan Wilkens, Juntao Luo, Yong Teng, Qinghe Meng and Yamin Li*, 
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Abstract

Among various mRNA carrier systems, lipid nanoparticles (LNPs) stand out as the most clinically advanced. While current clinical trials of mRNA/LNP therapeutics mainly address liver diseases, the potential of mRNA therapy extends far beyond─yet to be unraveled. To fully unlock the promises of mRNA therapy, there is an urgent need to develop safe and effective LNP systems that can target extrahepatic organs. Here, we report on the development of sulfonium lipid nanoparticles (sLNPs) for systemic mRNA delivery to the lungs. sLNP effectively and specifically delivered mRNA to the lungs following intravenous administration in mice. No evidence of lung and systemic inflammation or toxicity in major organs was induced by sLNP. Our findings demonstrated that the newly developed lung-specific sLNP platform is both safe and efficacious. It holds great promise for advancing the development of new mRNA-based therapies for the treatment of lung-associated diseases and conditions.

Abstract Image

Abstract Image

通过锍脂质纳米颗粒实现肺特异性 mRNA 传输
在各种 mRNA 载体系统中,脂质纳米颗粒(LNPs)是临床上最先进的一种。虽然目前 mRNA/LNP 疗法的临床试验主要针对肝脏疾病,但 mRNA 疗法的潜力远不止于此,还有待进一步发掘。为了充分释放 mRNA 疗法的潜力,我们迫切需要开发可针对肝外器官的安全有效的 LNP 系统。在此,我们报告了用于向肺部全身性递送 mRNA 的锍脂质纳米颗粒(sLNPs)的开发情况。小鼠静脉给药后,sLNP 能有效、特异地向肺部递送 mRNA。没有证据表明 sLNP 会诱发肺部和全身炎症或对主要器官产生毒性。我们的研究结果表明,新开发的肺特异性 sLNP 平台既安全又有效。它有望推动基于 mRNA 的新疗法的开发,用于治疗肺相关疾病和病症。
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来源期刊
Nano Letters
Nano Letters 工程技术-材料科学:综合
CiteScore
16.80
自引率
2.80%
发文量
1182
审稿时长
1.4 months
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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