Targeted glutamine-decorated chitosan nanoparticles with enhanced synergism of chemotherapeutic and natural medicine for hepatic carcinoma therapy

Abstract

Targeted delivery of therapeutic agents to malignant tumor sites is an effective strategy to improve the treatment outcomes for tumor precise therapy. Herein, based on the abnormal tumor metabolism (glutamine addiction), a nanosystem of glutamine-decorated nanoparticles was fabricated to achieve efficient tumor delivery. Considering the high toxicity and side effect by chemotherapy with high doses, a chemotherapeutic sensitizer tetrandrine was used in combination with doxorubicin to achieve a synergistic effect in tumor treatment. The targeted nanosystems of glutamine-decorated nanoparticles (GDTNPs) were loaded with doxorubicin and tetrandrine simultaneously. Effective tumor accumulation of GDTNPs in vitro and in vivo was achieved due to glutamine addiction and the extraordinary inter-organ glutamine metabolism. The data revealed that tetrandrine enhanced the efficacy of doxorubicin to hepatic carcinoma cells by blocking cell proliferation, inducing apoptosis, and arresting cell cycle, demonstrating the synergism of doxorubicin and tetrandrine. With KM mice bearing murine hepatic tumor (H22) as model, GDTNPs demonstrated the optimum tumor inhibition efficacy with no notable systemic toxicity. Therefore, it could be propose that the co-delivery of doxorubicin and tetrandrine by the glutamine-decorated nanoparticles is a promising strategy for the effective chemotherapy of hepatic carcinoma with enhanced efficacy and reduced cytotoxicity.

Keywords

• Glutamine addiction
• Nanoparticles
• Tumor-targeted delivery
• Synergistic therapy
• Tetrandrine