{"id":735,"date":"2025-11-24T11:53:06","date_gmt":"2025-11-24T03:53:06","guid":{"rendered":"https:\/\/xueqingzhang-lab.com\/?page_id=735"},"modified":"2026-04-14T21:25:58","modified_gmt":"2026-04-14T13:25:58","slug":"%e5%90%b8%e5%85%a5%e5%bc%8f%e7%ba%b3%e7%b1%b3%e8%bd%bd%e4%bd%93%e5%b0%86mrna%e9%80%92%e9%80%81%e8%87%b3%e7%ba%a4%e7%bb%b4%e5%8c%96%e8%82%ba%e9%83%a8%e5%b9%b6%e5%8f%91%e6%8c%a5%e6%8a%97%e7%ba%a4","status":"publish","type":"page","link":"https:\/\/xueqingzhang-lab.com\/en\/%e5%90%b8%e5%85%a5%e5%bc%8f%e7%ba%b3%e7%b1%b3%e8%bd%bd%e4%bd%93%e5%b0%86mrna%e9%80%92%e9%80%81%e8%87%b3%e7%ba%a4%e7%bb%b4%e5%8c%96%e8%82%ba%e9%83%a8%e5%b9%b6%e5%8f%91%e6%8c%a5%e6%8a%97%e7%ba%a4\/","title":{"rendered":"Research on inhalable nanocarriers for lung-targeted mRNA delivery and antifibrotic therapy in fibrotic lungs"},"content":{"rendered":"
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Research from Dr. Xueqing Zhang\u2019s group at Shanghai Jiao Tong University on inhalable lung targeted mRNA delivery was published in Nature Communications<\/h2>\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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\u00a0 \u00a0 \u00a0 \u00a0 Idiopathic pulmonary fibrosis (IPF) is one of the most common interstitial lung diseases, characterized by extensive fibrotic lesions and a mortality rate higher than that of many cancers. Current therapeutic agents for IPF, including pirfenidone and nintedanib, can only slow disease progression but are unable to reverse established fibrotic scars. Inhalable mRNA-based protein replacement therapy enables maximal drug accumulation in the lungs, allowing for the expression of virtually any desired protein or peptide, targeting \u201cundruggable\u201d pathways, and generating therapeutic antibody cocktails. This approach holds great promise for the treatment of respiratory diseases, including IPF. However, successful inhalable nucleic acid delivery systems must withstand shear stress during nebulization, penetrate mucus barriers, evade macrophage clearance, and ensure efficient cytoplasmic delivery and protein translation.<\/p>

\u00a0 \u00a0 \u00a0 \u00a0 Recently, the team published an article titled \u201cOptimized inhaled LNP formulation for enhanced treatment of idiopathic pulmonary fibrosis via mRNA-mediated antibody therapy\u201d in Nature Communications. In this study, the authors developed an inhalable nucleic acid nanocarrier capable of delivering mRNA to the lungs of fibrotic mice, thereby achieving antifibrotic therapeutic effects. Dr. Xin Bai from Shanghai Jiao Tong University is the first author, and the School of Pharmacy at Shanghai Jiao Tong University serves as both the primary and corresponding institution.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

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\u00a0 \u00a0 \u00a0 \u00a0 In this project, the researchers first proposed a novel \u201cLOOP\u201d platform, consisting of a four-step workflow that avoids extensive and redundant LNP screening. Using microfluidic technology, they prepared a series of LNPs composed of varying molar ratios of ionizable lipids, cholesterol, helper lipids, and PEG-lipids, from which formulations with optimal resistance to shear stress were selected. Subsequently, the dialysis system for these LNPs was optimized. Meanwhile, excipients such as alcohols and nonionic surfactants were introduced to enhance the resistance of LNPs to shear-induced damage during nebulization. Finally, based on the selected dialysis buffer and excipients, the molar ratios of lipid components were further tuned to investigate the structure\u2013activity relationship between lipid composition and luciferase expression. Ultimately, an optimized formulation, iLNP-HP08LOOP<\/sup>characterized by a high proportion of helper lipids, an acidic dialysis buffer, and excipients\u2014was identified, exhibiting superior nebulization stability and enhanced pulmonary luciferase expression.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

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\u5438\u5165\u5f0f\u80ba\u9776\u5411\u7597\u6cd5\u6cbb\u7597IPF\u7684\u793a\u610f\u56fe<\/h6>\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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        Based on this optimized iLNP-HP08LOOP<\/sup>delivery system, the researchers further loaded mRNA encoding an IL-11 single-chain antibody (scFv) to generate scFv@iLNP-HP08LOOP<\/sup>, thereby successfully developing an mRNA-mediated inhalable antibody therapy. Following administration via a vibrating mesh nebulizer, scFv@iLNP-HP08LOOP<\/sup>efficiently deposited in the lungs, where IL-11 scFv mRNA was locally released and subsequently translated into IL-11 scFv protein. The expressed antibody binds to overexpressed IL-11 in the pulmonary microenvironment through autocrine or paracrine mechanisms. In a bleomycin-induced pulmonary fibrosis mouse model, inhaled scFv@iLNP-HP08LOOP<\/sup>effectively inhibited fibroblast activation and extracellular matrix (ECM) production, demonstrating significantly superior efficacy compared to nebulized or intravenously administered IL-11 scFv protein. Pulmonary function tests further showed that inhaled scFv@iLNP-HP08LOOP<\/sup>significantly improved all lung function parameters in fibrotic mice. Notably, the HP08LOOP<\/sup>system also enhanced the nebulization stability and pulmonary luciferase expression of LNPs formulated with the clinically used ionizable lipid ALC0315.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

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\u00a0 \u00a0 \u00a0 \u00a0 In summary, the \u201cLOOP\u201d strategy provides a versatile platform for the development of other inhalable mRNA-based protein replacement therapies, offering broad prospects for the prevention and management of interstitial lung diseases (ILDs), including IPF, as well as other respiratory disorders.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

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Original article link:
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