LPA1 antagonist-derived LNPs deliver A20 mRNA and promote anti-fibrotic activities DOI Creative Commons
Jinyue Yan,

Diana D. Kang,

Chang Wang

et al.

Nano Research, Journal Year: 2024, Volume and Issue: 17(10), P. 9095 - 9102

Published: June 27, 2024

Abstract Activated fibroblasts are major mediators of pulmonary fibrosis. Fibroblasts generally found in the connective tissue but upon activation can generate excess extracellular matrix (ECM) lung interstitial section. Therefore, one most targeted cells for treating idiopathic fibrosis (IPF). Here, we develop an anti-fibrotic platform that modulate both lysophosphatidic acid receptor 1 (LPA ) and inflammatory pathway through tumor necrosis factor α -induced protein 3 (TNFAIP3, also known as A20) fibroblasts. First, synthesized a series LPA antagonists, AM095 AM966, derived amino lipids (LA lipids) which were formulated into LA-lipid nanoparticles (LA-LNPs) encapsulating mRNA. Specifically, LA5-LNPs, with AM966 head group biodegradable acetal lipid tails, showed efficient A20 mRNA delivery to vitro (80.2% ± 1.5%) ex vivo (17.2% 0.4%). When treated primary mouse (MLF), this formulation inhibited fibroblast migration collagen production, thereby slowing progression IPF. Overall, LA5-LNPs encapsulated is novel offering potential approach regulate treatment

Language: Английский

LPA1 antagonist-derived LNPs deliver A20 mRNA and promote anti-fibrotic activities DOI Creative Commons
Jinyue Yan,

Diana D. Kang,

Chang Wang

et al.

Nano Research, Journal Year: 2024, Volume and Issue: 17(10), P. 9095 - 9102

Published: June 27, 2024

Abstract Activated fibroblasts are major mediators of pulmonary fibrosis. Fibroblasts generally found in the connective tissue but upon activation can generate excess extracellular matrix (ECM) lung interstitial section. Therefore, one most targeted cells for treating idiopathic fibrosis (IPF). Here, we develop an anti-fibrotic platform that modulate both lysophosphatidic acid receptor 1 (LPA ) and inflammatory pathway through tumor necrosis factor α -induced protein 3 (TNFAIP3, also known as A20) fibroblasts. First, synthesized a series LPA antagonists, AM095 AM966, derived amino lipids (LA lipids) which were formulated into LA-lipid nanoparticles (LA-LNPs) encapsulating mRNA. Specifically, LA5-LNPs, with AM966 head group biodegradable acetal lipid tails, showed efficient A20 mRNA delivery to vitro (80.2% ± 1.5%) ex vivo (17.2% 0.4%). When treated primary mouse (MLF), this formulation inhibited fibroblast migration collagen production, thereby slowing progression IPF. Overall, LA5-LNPs encapsulated is novel offering potential approach regulate treatment

Language: Английский

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