Construction of mPEI/pGPX4 gene therapeutic system for the effective treatment of acute lung injury

Acute lung injury (ALI) can be induced by various injury factors, which is closely related to the inflammatory reaction and cellular ferroptosis reported recently. Glutathione peroxidase (GPX4) palys an important role in the inflammatory reaction, which also is the core regulatory protein of ferroptosis. Up-regulation of GPX4 can be helpful to inhibit the cellular ferroptosis and inflammatory reaction to treat ALI. mPEI/pGPX4 gene therapeutic system based on mannitol-modified polyethyleneimine (mPEI) was constructed. Compared with PEI/pGPX4 nanoparticles using commoditized gene vector PEI 25k, mPEI/pGPX4 nanoparticles achieved caveolae-mediated endocytosis and improved the gene therapeutic effect. mPEI/pGPX4 nanoparticles could up-regulate the gene expression of GPX4, inhibit inflammatory reaction and the cellular ferroptosis, thereby alleviating the ALI in vitro and in vivo. The finding indicated that gene therapy with pGPX4 is a potential therapeutic system for the effective treatment of ALI.

Automated summary

Acute lung injury (ALI) can be caused by various injury factors and is closely related to inflammatory reaction and cellular ferroptosis. GPX4 plays a crucial role in the inflammatory reaction and is the core regulatory protein of ferroptosis. The use of mPEI/pGPX4 nanoparticles, based on mannitol-modified polyethyleneimine (mPEI), could up-regulate the gene expression of GPX4, inhibit inflammatory reaction and cellular ferroptosis, effectively alleviating ALI in vitro and in vivo. This study suggests that gene therapy with pGPX4 holds potential as a therapeutic system for ALI treatment.