Folate-mediated inflammatory microenvironment-responsive nanocarriers for the delivery of Moringa A to target NLRP3 for the treatment of viral pneumonia.

Cytokine storm triggered by respiratory viral infection is the core pathogenic mechanism of severe pneumonia, and excessive activation of the NLRP3 inflammasome is a critical link in inducing this storm and subsequent lung tissue damage. This study targets the NLRP3 inflammasome to investigate the therapeutic effects, mechanisms of action, and targeted delivery advantages of folic acid-modified nanoparticles encapsulating Moringa A (MA NPs) for viral pneumonia. Utilizing techniques such as cellular experiments, mouse model validation, molecular docking, bio-layer interferometry (BLI), immunohistochemistry, immunofluorescence, and histopathology, this study systematically analyzed the effects of MA NPs on the NLRP3 inflammasome pathway, pyroptosis, macrophage polarization, and lung tissue injury, while also validating the targeting efficacy of the folic acid-modified nanodelivery system. The results showed that MA NPs significantly reduced the expression of NLRP3, ASC, Caspase-1, and GSDMD in H1N1 virus-infected cells, decreased the levels of pyroptosis-related cytokines, and MA was confirmed to be an NLRP3 inhibitor. In mouse models, MA NPs reduced the lung index, downregulated the expression of pro-inflammatory cytokines in lung tissue, and alleviated pathological and ultrastructural damage to lung tissue. Furthermore, MA NPs inhibited the excessive activation of the NLRP3 inflammasome and promoted the polarization of macrophages from the M1 phenotype to the M2 phenotype, thereby alleviating the pulmonary inflammatory microenvironment. Therefore, MA NPs can repair lung tissue damage by inhibiting excessive activation of the NLRP3 inflammasome and regulating macrophage polarization, and combined with the folic acid-targeted delivery system, achieve precision treatment for viral pneumonia. This provides a new approach and experimental basis for the synergistic intervention of viral pneumonia.