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Targeted Dual Small Interfering Ribonucleic Acid Delivery via Non‐Viral Polymeric Vectors for Pulmonary Fibrosis Therapy
Author(s) -
Ji Qijian,
Hou Jiwei,
Yong Xueqing,
Gong Guangming,
Muddassir Mohd.,
Tang Tianyu,
Xie Jinbing,
Fan Wenpei,
Chen Xiaoyuan
Publication year - 2021
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202007798
Subject(s) - nanocarriers , mesenchymal stem cell , small interfering rna , cancer research , myofibroblast , oncogene , materials science , pulmonary fibrosis , fibrosis , rna , cell , biology , drug delivery , microbiology and biotechnology , medicine , pathology , nanotechnology , cell cycle , biochemistry , gene
Inhibiting the myofibroblast differentiation of lung‐resident mesenchymal stem cells (LR‐MSCs) is a promising yet challenging approach for pulmonary fibrosis (PF) therapy. Here, micelles formed by a graft copolymer of multiple PEGs modified branched polyethylenimine are used for delivering runt‐related transcription factor‐1 (RUNX1) small interfering RNA (siRNA) (siRUNX1) to the lung, aiming to inhibit the myofibroblast differentiation of LR‐MSCs. LR‐MSC targeting is achieved by functionalizing the micelle surface with an anti‐stem‐cell antigen‐1 antibody fragment (Fab′). Consequently, therapeutic benefits are obtained by successful suppression of myofibroblast differentiation of LR‐MSCs in bleomycin‐induced PF model mice treated with siRUNX1‐loaded micelles. Furthermore, an excellent synergistic effect of PF therapy is achieved for this micelle system loaded siRUNX1 and glioma‐associated oncogene homolog‐1 (Gli1) small interfering RNA (siGli1), a traditional anti‐PF siRNA of glioma‐associated oncogene homolog‐1. Hence, this work not only provides RUNX1 as a novel PF therapeutic target, but also as a promising dual siRNA‐loaded nanocarrier system for the therapy of PF.