DataVXAdvanced MaterialsPaper
journal article·2022-04

Inhaled mRNA Nanoformulation with Biogenic Ribosomal Protein Reverses Established Pulmonary Fibrosis in a Bleomycin‐Induced Murine Model

Rui Zhang, Weiqiang Jing, Chen Chen, Shengchang Zhang, Mohnad Abdalla, Peng Sun, Ganyu Wang, Wenjie You, Zhenmei Yang, Jing Zhang, Chunwei Tang, Wei Du, Ying Liu, Xiaoxun Li, Jitian Liu, Xiaona You, Huili Hu, Lei Cai, Fengbo Xu, Baixiang Dong, Minglu Liu, Bangming Qiang, Yanhua Sun, Gongchang Yu, Jibiao Wu, Kun Zhao, Xinyi Jiang

Advanced Materials· Volume 34· Issue 14
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Source abstract

Abstract

Abstract Idiopathic pulmonary fibrosis (IPF), a lethal respiratory disease with few treatment options, occurs due to repetitive microinjuries to alveolar epithelial cells (AECs) and progresses with an overwhelming deposition of extracellular matrix (ECM), ultimately resulting in fibrotic scars and destroyed the alveolar architecture. Here, an inhaled ribosomal protein‐based mRNA nanoformulation is reported for clearing the intrapulmonary ECM and re‐epithelializing the disrupted alveolar epithelium, thereby reversing established fibrotic foci in IPF. The nanoformulation is sequentially assembled by a ribosomal protein‐condensed mRNA core, a bifunctional peptide‐modified corona and keratinocyte growth factor (KGF) with a PEGylated shielding shell. When inhaled via a nebulizer, the nanoformulations carried by microdrops are deposited in the alveoli, and penetrate into fibrotic foci, where the outer KGFs are detached after matrix metalloproteinase 2 (MMP2) triggering. The RGD motif‐grafted cores then expose and specifically target the integrin‐elevated cells for the intracellular delivery of mRNA. Notably, repeated inhalation of the nanoformulations accelerates the clearance of locoregional collagen by boosting the intralesional expression of MMP13 and alveolar re‐epithelialization mediated by KGFs, which synergistically ameliorates the lung function of a bleomycin‐induced murine model. Therefore, this work provides an alternative mRNA‐inhalation delivery strategy, which shows great potential for the treatment of IPF.
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Research context

NanomaterialsMaterials processing

OpenAlex topics: Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis · Inhalation and Respiratory Drug Delivery · Occupational exposure and asthma

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education) Department of Pharmaceutics School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 China

Department of Urology Qilu Hospital Cheeloo College of Medicine Shandong University Jinan 250012 China

Shandong University of Traditional Chinese Medicine Jinan 250355 China

Department of Respiratory and Critical Care Medicine Shandong Provincial Hospital Cheeloo College of Medicine Shandong University Jinan 250021 China

Experimental Teratology Ministry of Education and Department of Molecular Medicine and Genetics School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 China

Shandong Provincial Key Laboratory of Biosensors, Biology Institute Qilu University of Technology Jinan 250103 China

Yinfeng Biological Group Co., LTD. Jinan 250102 China

Bellastem Biotechnology Limited Gaomi 261500 China

Shandong Provincial Key Laboratory of Microparticles Drug Delivery Technology Qilu Pharmaceutical Co., LtD Jinan 250100 China

Neck‐Shoulder and Lumbocrural Pain Hospital Shandong First Medical University & Shandong Academy of Medical Sciences Jinan 250012 China

Funding

National Natural Science Foundation of China

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