Your browser doesn't support javascript.
loading
Lymphatic endothelial cell-targeting lipid nanoparticles delivering VEGFC mRNA improve lymphatic function after injury.
Michalaki, Eleftheria; Chin, Rachel; Jeong, Kiyoung; Qi, Zhiming; Liebman, Lauren N; González-Vargas, Yarelis; Echeverri, Elisa Schrader; Paunovska, Kalina; Muramatsu, Hiromi; Pardi, Norbert; Tamburini, Beth Jiron; Jakus, Zoltan; Dahlman, James E; Dixon, J Brandon.
Afiliación
  • Michalaki E; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology; Atlanta, GA, USA.
  • Chin R; Department of Biology, Georgia Institute of Technology; Atlanta, GA, USA.
  • Jeong K; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University; Atlanta, GA, USA.
  • Qi Z; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University; Atlanta, GA, USA.
  • Liebman LN; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University; Atlanta, GA, USA.
  • González-Vargas Y; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University; Atlanta, GA, USA.
  • Echeverri ES; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University; Atlanta, GA, USA.
  • Paunovska K; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University; Atlanta, GA, USA.
  • Muramatsu H; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA.
  • Pardi N; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, USA.
  • Tamburini BJ; University of Colorado School of Medicine, Department of Medicine, Aurora, CO, USA.
  • Jakus Z; Semmelweis University School of Medicine, Department of Physiology, Budapest, Hungary.
  • Dahlman JE; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University; Atlanta, GA, USA.
  • Dixon JB; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology; Atlanta, GA, USA.
bioRxiv ; 2024 Jul 31.
Article en En | MEDLINE | ID: mdl-39131391
ABSTRACT
Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Advances in targeted therapy have shown promise for treating diseases where conventional therapies have been ineffective and lymphatic vessels have recently emerged as a new therapeutic target. Lipid nanoparticles (LNPs) have emerged as a promising strategy for tissue specific delivery of nucleic acids. Currently, there are no approaches to target LNPs to lymphatic endothelial cells, although it is well established that intradermal (ID) injection of nanoparticles will drain to lymphatics with remarkable efficiency. To design an LNP that would effectively deliver mRNA to LEC after ID delivery, we screened a library of 150 LNPs loaded with a reporter mRNA, for both self-assembly and delivery in vivo to lymphatic endothelial cells (LECs). We identified and validated several LNP formulations optimized for high LEC uptake when administered ID and compared their efficacy for delivery of functional mRNA with that of free mRNA and mRNA delivered with a commercially available MC3-based LNP (Onpattro™). The lead LEC-specific LNP was then loaded with VEGFC mRNA to test the therapeutic advantage of the LEC-specific LNP (namely, LNP7) for treating a mouse tail lymphatic injury model. A single dose of VEGFC mRNA delivered via LNP7 resulted in enhanced LEC proliferation at the site of injury, and an increase in lymphatic function up to 14-days post-surgery. Our results suggest a therapeutic potential of VEGFC mRNA lymphatic-specific targeted delivery in alleviating lymphatic dysfunction observed during lymphatic injury and could provide a promising approach for targeted, transient lymphangiogenic therapy.
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos