Chitosan nanoparticles loaded with aspirin and 5-fluororacil enable synergistic antitumor activity through the modulation of NF-κB/COX-2 signaling pathways

Based on the enhancement of synergistic antitumour activity to treat cancer and the correlation between inflammation and carcinogenesis, the authors designed chitosan nanoparticles for co-delivery of 5-fluororacil (5-Fu: an as anti-cancer drug) and aspirin (a non-steroidal anti-inflammatory drug) and induced synergistic antitumour activity through the modulation of the nuclear factor kappa B (NF-κB)/cyclooxygenase-2 (COX-2) signalling pathways. The results showed that aspirin at non-cytotoxic concentrations synergistically sensitised hepatocellular carcinoma cells to 5-Fu in vitro. It demonstrated that aspirin inhibited NF-κB activation and suppressed NF-κB regulated COX-2 expression and prostaglandin E2 (PGE2) synthesis. Furthermore, the proposed results clearly indicated that the combination of 5-Fu and aspirin by chitosan nanoparticles enhanced the intracellular concentration of drugs and exerted synergistic growth inhibition and apoptosis induction on hepatocellular carcinoma cells by suppressing NF-κB activation and inhibition of expression of COX-2.