Chinese scientists have developed a novel nanotherapy known as biomimetic extracellular vesicle spherical nucleic acids (BEV-SNAs), which has shown efficacy in treating idiopathic pulmonary fibrosis (IPF). This study was published in the journal Aggregate.
IPF is a fatal disease characterized by irreversible lung scarring, affecting over five million patients worldwide, with a median survival of only three to five years. Current treatments for IPF, such as nintedanib and pirfenidone, which are approved by the U.S. Food and Drug Administration (FDA), only moderately slow disease progression without significantly extending survival.
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown therapeutic potential, but they face challenges like low production yield, functional variability, and poor delivery efficiency to lung tissues, which limits their clinical application.
To address these challenges, researchers from the Ningbo Institute of Materials Technology and Engineering (NIMTE) of the Chinese Academy of Sciences, in collaboration with their partners, have designed and synthesized a lung-penetrating BEV-SNA platform for IPF therapy. The team integrated mechanically produced BEVs from primary mesenchymal stem cells with cholesterol-modified DNA through hydrophobic assembly, leading to a three-dimensional (3D) architecture.
"This dense 3D DNA structure can reduce mucus adhesion, thereby enhancing airway penetration and facilitating efficient cellular uptake in deep lung tissues," said Prof. WANG Kaizhe, a corresponding author of the study.
In this study, the BEV-SNA platform achieves a 17.2-fold increase in vesicle production compared to natural extracellular vesicles.
In mouse models, BEV-SNA demonstrated impressive therapeutic effects at various stages. The treatment effectively cleared reactive oxygen species (ROS) to protect alveolar cells, reduced pro-inflammatory cytokines to suppress inflammation, and inhibited collagen deposition to combat fibrosis. This therapy resulted in a 50% survival rate in treated groups, significantly outperforming untreated controls.
This study presents a dual-action strategy that addresses the ROS-inflammation-fibrosis cycle while enabling effective delivery to deep lung tissues. It may pave the way for innovative treatments for respiratory diseases and advancements in biomimetic nanomedicine design.
BEV-SNA-mediated therapy for idiopathic pulmonary fibrosis. (Image by NIMTE)