In vivo mechanisms of resveratrol liposomes in targeting the TLR4/NLRP3 pathway in lung cancer

The TLR4/NLRP3 inflammasome pathway drives lung cancer cell proliferation, migration, and invasiveness. However, no in vivo treatments targeting this pathway in lung cancer exist. Resveratrol, an anti-inflammatory compound, inhibits the NLRP3 inflammasome but requires high doses due to its hydrophobicity and instability. This study aimed to enhance the therapeutic efficacy of resveratrol by encapsulating it in liposomes to effectively target the TLR4/NLRP3 inflammasome pathway in lung cancer. In this study, the efficacy of resveratrol liposome was tested in vitro through cell proliferation and migration assays and gene expression analysis. In vivo effects were evaluated in a lung cancer mouse model using histological and molecular techniques. Resveratrol liposome significantly inhibited lung cancer cell proliferation and migration, and induced apoptosis in orthotopic lung cancer models. Additionally, by suppressing TLR4/NLRP3 inflammasome-related genes, resveratrol liposomes diminished levels of IL-1β and IL-18 both locally at tumor sites and systemically, thus modulating the tumor immune microenvironment by decreasing MDSCs and increasing CD4⁺ and CD8⁺ T cells. In conclusion, resveratrol liposome alleviates lung cancer progression by targeting the TLR4/NLRP3 inflammasome pathway and enhancing anti-tumor immune responses, highlighting its potential as a promising therapeutic strategy for lung cancer treatment.