Jingyue Yan, Diana D. Kang, Chang Wang, Xucheng Hou, Shi Du, Siyu Wang, Yonger Xue, Zhengwei Liu, Haoyuan Li, Yichen Zhong, Binbin Deng, David W. McComb, Yizhou Dong
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引用次数: 0
Abstract
Activated fibroblasts are major mediators of pulmonary fibrosis. Fibroblasts are generally found in the connective tissue but upon activation can generate excess extracellular matrix (ECM) in the lung interstitial section. Therefore, fibroblasts are one of the most targeted cells for treating idiopathic pulmonary fibrosis (IPF). Here, we develop an anti-fibrotic platform that can modulate both the lysophosphatidic acid receptor 1 (LPA1) and the inflammatory pathway through tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) in fibroblasts. First, we synthesized a series of LPA1 antagonists, AM095 and AM966, derived amino lipids (LA lipids) which were formulated into LA-lipid nanoparticles (LA-LNPs) encapsulating mRNA. Specifically, LA5-LNPs, with AM966 head group and biodegradable acetal lipid tails, showed efficient A20 mRNA delivery to lung fibroblasts in vitro (80.2% ± 1.5%) and ex vivo (17.2% ± 0.4%). When treated to primary mouse lung fibroblasts (MLF), this formulation inhibited fibroblast migration and collagen production, thereby slowing the progression of IPF. Overall, LA5-LNPs encapsulated with A20 mRNA is a novel platform offering a potential approach to regulate fibroblast activation for the treatment of IPF.
期刊介绍:
Nano Research is a peer-reviewed, international and interdisciplinary research journal that focuses on all aspects of nanoscience and nanotechnology. It solicits submissions in various topical areas, from basic aspects of nanoscale materials to practical applications. The journal publishes articles on synthesis, characterization, and manipulation of nanomaterials; nanoscale physics, electrical transport, and quantum physics; scanning probe microscopy and spectroscopy; nanofluidics; nanosensors; nanoelectronics and molecular electronics; nano-optics, nano-optoelectronics, and nano-photonics; nanomagnetics; nanobiotechnology and nanomedicine; and nanoscale modeling and simulations. Nano Research offers readers a combination of authoritative and comprehensive Reviews, original cutting-edge research in Communication and Full Paper formats. The journal also prioritizes rapid review to ensure prompt publication.