Discover how the innovative co-delivery of siNRF2 and Sorafenib via a cutting-edge hyperbranched nanocarrier is revolutionizing the treatment of hepatocellular carcinoma by synergistically inducing ferroptosis.
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Co-Delivery of siNRF2 and Sorafenib by a “Click” Dual Functioned Hyperbranched Nanocarrier for Synergistically Inducing Ferroptosis in Hepatocellular Carcinoma.
Tong et al., Small 2023
DOI: 10.1002/smll.202307273
The study introduces a novel pH-responsive, amphiphilic hyperbranched polyglycerol (HDP) synthesized via a co-graft click chemistry pathway. This nanocarrier is designed to co-deliver sorafenib, an anti-cancer drug, and siRNA targeting nuclear factor erythroid-2 related factor 2 (NRF2), which is known to induce drug resistance through ferroptosis resistance. The HDP nanocarrier exhibits excellent drug-loading capacity, storage stability, and pH responsiveness.
Key findings include the synergistic effect of sorafenib and siNRF2 in inducing reactive oxygen species (ROS), iron overload, glutathione (GSH) depletion, and lipid peroxidation, leading to enhanced anti-tumor activity. In animal experiments, the HDP loaded with both siNRF2 and sorafenib (HDP-ss) achieved a remarkable tumor inhibition rate of approximately 94%.
Significance: This research is important as it presents a promising strategy to overcome drug resistance in tumor therapy, particularly resistance to antiangiogenic therapy and ferroptosis. The use of HDP as a targeted delivery system, combined with siNRF2, significantly improves the efficacy of sorafenib, offering a potential new approach to cancer treatment.