Emerging gene delivery nanosystems for the treatment of acute lung injury

Acute lung injury (ALI) is an inflammatory phenomenon characterized by hypoxia and edema. When the lungs are damaged, inflammation begins due to pro-inflammatory cytokines secreted by macrophages in the alveoli. In addition, neutrophils infiltrate the lung tissue, inducing additional inflammation. Accumulation of plasma proteins and fluids in the alveoli causes severe hypoxia and respiratory failure. Current treatments include anti-inflammatory drugs such as steroids and mechanical ventilation; however, these treatments have transient effects and may be accompanied by significant deleterious side effects, increasing mortality rate. This suggests that new therapeutic modalities should be developed for effective treatment of ALI. Recently, gene therapy for ALI was proposed as a novel treatment for ALI. Therapeutic genes such as anti-inflammatory genes and siRNAs/miRNAs have been evaluated for suppression of inflammatory reactions. The results have indicated that efficient carriers for gene delivery need to be developed. Various nanosystems for delivery of therapeutic genes to the lungs, including polymers, lipid nanoparticles, exosomes, and cell membrane-based nanovesicles, have been investigated. In this review, an in-depth analysis of gene delivery nanosystems for ALI treatment is presented with major achievements and challenges for future development. PubMed and Google Scholar were used as resources for searching related literature.