Research on Therapeutic Strategy of Inhalable Cell Membrane-Coated Nanodelivery Complexes Mediating Nrf2 Pathway for...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pulmonary Medicine

Background:

• Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease driven by oxidative stress and inflammation.
• Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of antioxidant responses, making it a therapeutic target.
• M2 macrophage polarization and ADORA2B receptor signaling promote fibrosis by increasing profibrotic mediators like TGF-β.

Purpose of the Study:

• To develop an inhaled biomimetic nanodelivery system for codelivering mulberrin and ADORA2B-targeted siRNA.
• To investigate the therapeutic potential of this system in ameliorating lung injury and fibrosis.

Main Methods:

• Fabrication of M2 macrophage membrane-coated nanoparticles (Mul-siRNA@MM) for codelivery of mulberrin and ADORA2B siRNA.
• Inhalation delivery of nanoparticles in a bleomycin-induced mouse model of lung fibrosis.
• Assessment of oxidative stress markers (ROS), Nrf2 pathway activation, ADORA2B expression, M2 macrophage infiltration, and fibrotic mediator release.

Main Results:

• Inhaled Mul-siRNA@MM nanoparticles suppressed ROS production by activating the Nrf2 pathway.
• The treatment effectively silenced ADORA2B expression, reducing M2 macrophage infiltration and profibrotic cytokine release.
• Significant amelioration of bleomycin-induced lung injury and fibrosis was observed in mice.

Conclusions:

• Inhaled biomimetic nanoparticles offer a targeted, safe, and effective strategy for IPF intervention.
• Disrupting the crosstalk between oxidative stress and pro-fibrotic signaling pathways is therapeutically valuable for IPF.
• Mulberrin and ADORA2B-targeted siRNA codelivery via inhaled nanoparticles shows promise for treating pulmonary fibrosis.