{"title":"Simplified Lipid Nanoparticles for Tissue- And Cell-Targeted mRNA Delivery Facilitate Precision Tumor Therapy in a Lung Metastasis Mouse Model.","authors":"Yuan Fei, Xiaolu Yu, Peiyu Liu, Hongyu Ren, Tuo Wei, Qiang Cheng","doi":"10.1002/adma.202409812","DOIUrl":null,"url":null,"abstract":"<p><p>mRNA-based applications have achieved remarkable success in the development of next-generation vaccines and the treatment of diverse liver diseases. Overcoming the challenge of delivering mRNA to extrahepatic tissues, especially specific cells within tissues, is crucial for precision therapy. In this study, a platform is developed for selective mRNA delivery to desired cells within tissues by combining lipid nanoparticle (LNP)-based targeted delivery with mRNA sequence-controlled expression. Through systematic optimization, a three-component LNP platform is developed, enabling targeted mRNA delivery to the lung, liver, and spleen. The incorporation of unique microRNA target sites into the mRNA scaffold further enhances control over protein translation in specific cells within the target tissue. This combined strategy, named SELECT (Simplified LNP with Engineered mRNA for Cell-type Targeting), demonstrates its efficacy in distinguishing mRNA expression between tumor and normal cells based on intracellular microRNA abundance. SELECT encapsulating mRNA encoding a tumor-specific cytotoxic protein, human ELANE, exhibits selective mRNA delivery to tumor lesions and significant inhibition of tumor growth in a mouse model of melanoma lung metastasis. Overall, SELECT has great potential as a new precision tumor treatment approach and also offers promising prospects for other mRNA therapies targeting specific cell types.</p>","PeriodicalId":114,"journal":{"name":"Advanced Materials","volume":null,"pages":null},"PeriodicalIF":27.4000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Materials","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/adma.202409812","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
mRNA-based applications have achieved remarkable success in the development of next-generation vaccines and the treatment of diverse liver diseases. Overcoming the challenge of delivering mRNA to extrahepatic tissues, especially specific cells within tissues, is crucial for precision therapy. In this study, a platform is developed for selective mRNA delivery to desired cells within tissues by combining lipid nanoparticle (LNP)-based targeted delivery with mRNA sequence-controlled expression. Through systematic optimization, a three-component LNP platform is developed, enabling targeted mRNA delivery to the lung, liver, and spleen. The incorporation of unique microRNA target sites into the mRNA scaffold further enhances control over protein translation in specific cells within the target tissue. This combined strategy, named SELECT (Simplified LNP with Engineered mRNA for Cell-type Targeting), demonstrates its efficacy in distinguishing mRNA expression between tumor and normal cells based on intracellular microRNA abundance. SELECT encapsulating mRNA encoding a tumor-specific cytotoxic protein, human ELANE, exhibits selective mRNA delivery to tumor lesions and significant inhibition of tumor growth in a mouse model of melanoma lung metastasis. Overall, SELECT has great potential as a new precision tumor treatment approach and also offers promising prospects for other mRNA therapies targeting specific cell types.
期刊介绍:
Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.