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Cationic cholesterol-dependent LNP delivery to lung stem cells, the liver, and heart.
Radmand, Afsane; Kim, Hyejin; Beyersdorf, Jared; Dobrowolski, Curtis N; Zenhausern, Ryan; Paunovska, Kalina; Huayamares, Sebastian G; Hua, Xuanwen; Han, Keyi; Loughrey, David; Hatit, Marine Z C; Del Cid, Ada; Ni, Huanzhen; Shajii, Aram; Li, Andrea; Muralidharan, Abinaya; Peck, Hannah E; Tiegreen, Karen E; Jia, Shu; Santangelo, Philip J; Dahlman, James E.
Affiliation
  • Radmand A; Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332.
  • Kim H; Department of Chemical Engineering, Georgia Institute of Technology, Atlanta, GA 30332.
  • Beyersdorf J; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Dobrowolski CN; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Zenhausern R; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Paunovska K; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Huayamares SG; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Hua X; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Han K; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Loughrey D; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Hatit MZC; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Del Cid A; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Ni H; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Shajii A; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Li A; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Muralidharan A; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Peck HE; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332.
  • Tiegreen KE; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332.
  • Jia S; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Santangelo PJ; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
  • Dahlman JE; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332.
Proc Natl Acad Sci U S A ; 121(11): e2307801120, 2024 Mar 12.
Article in En | MEDLINE | ID: mdl-38437539
ABSTRACT
Adding a cationic helper lipid to a lipid nanoparticle (LNP) can increase lung delivery and decrease liver delivery. However, it remains unclear whether charge-dependent tropism is universal or, alternatively, whether it depends on the component that is charged. Here, we report evidence that cationic cholesterol-dependent tropism can differ from cationic helper lipid-dependent tropism. By testing how 196 LNPs delivered mRNA to 22 cell types, we found that charged cholesterols led to a different lungliver delivery ratio than charged helper lipids. We also found that combining cationic cholesterol with a cationic helper lipid led to mRNA delivery in the heart as well as several lung cell types, including stem cell-like populations. These data highlight the utility of exploring charge-dependent LNP tropism.
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Full text: 1 Database: MEDLINE Main subject: Stem Cells / Liver Language: En Year: 2024 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Stem Cells / Liver Language: En Year: 2024 Type: Article