Randomized trial demonstrates enhanced tumor suppression in hepatocellular carcinoma through lactate metabolic reprogramming.
Key Points
The aim is to investigate the effectiveness of a novel nanoplatform in enhancing copper-induced cell death in liver cancer by reprogramming metabolism.
Synthesized LOX/LDHi-Cu NP via dopamine polymerization with Cu²⁺ chelation; characterized for size and dynamics.
In vitro analysis on HepG2 and Huh-7 cells treated with the nanoplatform using lactate supplementation.
In vivo evaluation on orthotopic HCC-bearing mice regarding lactate levels, Cu accumulation, and tumor growth.
LOX/LDHi-Cu NP effectively scavenged lactate and reinstated oxidative phosphorylation, leading to increased cuproptotic death.
Significant reduction in intratumoral lactate and robust tumor suppression was observed in vivo without systemic toxicity.
Immunogenic cell death and enhanced copper-dependent protein aggregation were confirmed as key effects of the intervention.