Synergistic targeting: Folate-glycyrrhetinic acid co-modified nanostructured lipid carrier enhances ampelopsin delivery to hepatic cancer cells

Ampelopsin (AMP) is a significant flavonoid compound known for its pharmacological properties, including anti-liver cancer and anti-liver fibrosis effects. However, its instability in the bloodstream and low bioavailability pose challenges in maintaining effective concentrations. To address this issue, this study developed a novel targeted drug delivery system: a nanostructured lipid carrier modified with Glycyrrhetinic acid (GA) and Folic acid (FA), loaded with AMP, termed GA/FA-AMP-NLC. This formulation leverages the specific recognition of FA and GA by tumor cells, facilitating both active and passive dual targeting of AMP to liver tumors. GA/FA-AMP-NLC was prepared using an organic solvent method, yielding particles with an average size of 130.30 ± 1.83 nm, a negatively charged surface, and a spherical morphology. The cellular uptake and cell viability of these lipid nanoparticles were examined in Hepa1–6 tumor-bearing mice, and their anti-tumor effects and in vivo tissue distribution were analyzed. Results from MTT assays indicated that GA/FA-AMP-NLC significantly inhibited the growth of HepG2 cells, demonstrating superior efficacy compared to FA-AMP-NLC and GA-AMP-NLC (p < 0.05). In vivo targeting tests and tissue distribution analyses confirmed that GA/FA-AMP-NLC effectively targets tumor sites and inhibits tumor growth while maintaining good biocompatibility. This formulation achieves both active and passive targeting of liver tumor sites via ligand connections, effectively eradicating tumor cells and offering a promising avenue for the development of AMP-targeted therapies.