A novel GHH copolymer was synthesized using hyaluronic acid modified with glycyrrhetinic acid and L‑histidine (His), and doxorubicin‑loaded GHH nanoparticles (DOX/GHH) were prepared for liver‑targeted drug delivery and pH‑responsive drug release. In the present study, GHH nanoparticles were characterized, and their pH‑responsive behaviors were evaluated at different pH levels. The antitumor effect of the DOX/GHH nanoparticles was investigated in vitro and in vivo. Results showed that the DOX/GHH nanoparticles were spherical, and the particle sizes ranged from 238.1 to 156.7 nm with an increase in the degree of substitution of His. The GHH nanoparticles were obviously internalized into human hepatoblastoma cells. In vitro cytotoxicity assay results showed that the DOX/GHH nanoparticles exhibited a dose‑dependent antitumor effect. Compared with free DOX, the DOX/GHH nanoparticles displayed higher antitumor efficacy. These results indicate that GHH nanoparticles could be a promising nano‑delivery carrier of hydrophobic drugs for liver‑targeted therapy.
Keywords: hyaluronic acid; nanoparticles; liver-targeting; pH-responsive.