Fig. 1: Development of phosphoramide lipid (PL) library for lung targeting RNA delivery and their inflammation evaluation. | Nature Communications

Fig. 1: Development of phosphoramide lipid (PL) library for lung targeting RNA delivery and their inflammation evaluation.

From: Boosting RNA nanotherapeutics with V-ATPase activating non-inflammatory lipid nanoparticles to treat chronic lung injury

Fig. 1: Development of phosphoramide lipid (PL) library for lung targeting RNA delivery and their inflammation evaluation.The alternative text for this image may have been generated using AI.

a Schematic of phosphorus oxychloride-mediated multicomponent reactions (PMR) in the synthesis of PLs. RT: Room temperature. b, c Structures of the three components of PLs used in the synthesis library and the screening process. d Preparation of PL LNPs by a microfluidic device. e Expression of mLuc at 6 h after intratracheal administration of the PL LNPs, the original MC3, ALC-0315, or cKK-E12 LNPs (0.2 mg/kg, n = 3 mice, one representative mouse in each group were shown). f Quantification of (e). g Schematic illustration of lipid nanoparticle (LNP) induced lung inflammation and collection of bronchoalveolar lavage (BAL). h Correlation analysis between cytokine secretion and mLuc expression after intratracheal administration of the PL LNPs. Measurement of IL-1β, IL-6, and TNF-α concentration were conducted using ELISA assay in BAL collected at 24 h after intratracheal administration of the PL LNPs (n = 3 mice in each group, mean values were presented). i Schematic shows the positive correlation of cytokine concentration and luciferase expression. j Chemical structure of PL32. k Gross anatomical images and H&E staining of lungs from healthy mice and ALI mice intratracheally instilled with PBS or single dose 0.6 mg/kg of mLuc in MC3 LNPs, ALC-0315 LNPs, and PL32 LNPs. n = 3 mice per group with similar results. Scale bar, 100 μm. Arrows indicate the areas of hepatization and inflammation. l Survival curve of bleomycin induced pulmonary fibrosis mice after two doses of mLuc LNPs treatment (0.6 mg/kg, n = 8 mice in each group). Data were represented as mean ± SEM. Figure (a, c, d, g, i, l) were created in BioRender. com with attribution line Miao, L. (2025) https://BioRender.com/p99f207, Miao, L. (2025) https://BioRender.com/a31ebmk, Miao, L. (2025) https://BioRender.com/g9lq68b, Miao, L. (2025) https://BioRender.com/kfsouj6, Miao, L. (2025) https://BioRender.com/v99qgqe and Miao, L. (2025) https://BioRender.com/qrqgh2s, respectively. Source data are provided as a Source Data file.

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