Engineered Lipid Nanoparticles for the Treatment of Pulmonary Fibrosis by Regulating Epithelial-Mesenchymal Transition in the Lungs

Hee Jin, Michaela Jeong, Gyeongseok Lee, Minjeong Kim, Youngjo Yoo, Hyun Jin Kim, Jaeho Cho, Yun Sil Lee, Hyukjin Lee

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Pulmonary fibrosis is a chronic and irreversible lung disease with limited therapeutic regimens. Advances in elucidating the pathophysiological mechanism and discovering novel therapeutic interventions are still in urgent need. Here, the engineered lipid nanoparticles (LNPs) are developed for delivering RNA therapeutics to the lungs. Three different types of LNPs (native, cationic, and ligand incorporated) are optimized to facilitate the pulmonary delivery of RNAs. Among them, the mannose incorporated LNPs (Mannose LNPs) outperform the others and show efficient delivery of siRNAs down-regulating the epithelial-mesenchymal transition (EMT) associated protein, G2 and S phase-expressed protein 1 (GTSE1). Treatment with the mannose LNPs confirms a significant decrease in collagen accumulation and EMT-related proteins in the fibrosis animal models and provides functional recovery from pulmonary fibrosis. This approach demonstrates that engineered LNPs can facilitate the delivery of RNA therapeutics to the lungs and potentially open a new regimen of treatment for pulmonary fibrosis.

Original languageEnglish
Article number2209432
JournalAdvanced Functional Materials
Volume33
Issue number7
DOIs
StatePublished - 9 Feb 2023

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF): 2018R1A5A2025286, 2022M3A9H1014125, 2020R1A2C2004364 funded by the Korean government (Ministry of Science and ICT): 2020M2D9A2093974, 2022M3E5F1081328, 2018M3A9H3020844 supported by the Korean government (Ministry of Food and Drug Safety): DY0002259453, and the Korea government (KDCA): 2021ER240300.

Publisher Copyright:
© 2022 Wiley-VCH GmbH.

Keywords

  • GTSE1
  • lipid nanoparticles
  • pulmonary fibrosis
  • RNA therapeutics

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