Identification Of Two Novel Small Compounds That Inhibit Liver Cancer Formation In Zebrafish And Analysis Of Their Conjugation To Nanodiamonds To Further Reduce Toxicity

Liver cancer, which is ranked fourth in cancer-related mortality worldwide, lacks effective therapeutic treatments. The development of new targeted therapies for liver cancer is urgently needed. The zebrafish is an excellent preclinical model organism for drug screening. Therefore, in a zebrafish model, hundreds of small molecules are screened, and two compounds (LIB1O0078 and LIB1O0144) are identified as the strongest inducers of antiangiogenic effects without side effects. LIB1O0078 exhibits better antiproliferation ability, and LIB1O0144 has better antimigration ability, as shown by xenotransplantation assays. Furthermore, LIB1O0078 and LIB1O0144 exhibit anti-HCC effects after retro-orbital injection into adult Tg(fabp10a:HBx,Src, p53-) triple transgenic fish with obesity and liver cancer. Because of the embryonic toxicity induced by these compounds, they are conjugated with nanodiamonds (ND), which are highly biocompatible function-based carriers. ND-coated small molecules not only reduce the embryonic toxicity and hepatotoxicity of the compounds, also exhibit better anti-HCC effects when administered by oral gavage in adult Tg(fabp10a:HBx,Src, p53-) fish with obesity and liver cancer. This study integrates nanotechnology and biomedical technology, identifies new potential anticancer drugs, and demonstrates the effectiveness of coating them on nanodiamonds in vivo. Facilitated by such a rapid zebrafish screening system, new anticancer drugs can be identified in a personalized and timely manner.