Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated death worldwide and is very difficult to treat using conventional chemotherapeutic drugs such as doxorubicin. Other common drugs, such as epirubicin, cisplatin, 5-fluorouracil, etoposide – and combinations of these – are even less effective. The only molecularly targeted drug available, sorafenib, is expenisve, and only marginally effective.

A team led by Taeghwan Hyeon of Seoul National University is now saying that it has screened a library containing hundreds of compounds against a panel of HCC cells and found that triptolide seems to be better than all previously tried therapies. Researchers have already found that this naturally occurring compound (which is isolated from the Tripterygium wilfordii plant) is very effective against many malignant cancer types including pancreatic cancer, neuroblastoma and cholangiocarcinoma. However, the downside is that in its uncoated form, it does not just target cancer cells and so is very toxic. By coating it with folate, Hyeon and colleagues have now overcome this problem.

The researchers began by esterfying pluronic F127 polymer with folate to make the coating material. They then polymerized β-benzyl-L-aspartate N-carboxy anhydride to make the core material pH sensitive. “The two polymers form a core/shell structured nanoparticle in water,” Hyeon tells nanotechweb.org, “and we loaded triptolide into the hydrophobic core to produce a nanoformulated gel version of the triptolide (that we call Nf-Trip).”

In experiments on mice with HCC, the team found that its coated triptolide accumulated in inflamed tumour tissue. Once there, the folate target ligand helps the HCC cells take up the anticancer drug. Since the fluid inside tumour cells is more acidic (with a pH of around 6.8) compared with normal tissue (which has a pH of about 7), the drop in pH causes the coating to fall away, so releasing the pure form of the triptolide, which then destroys the tumour cells.

The team, which includes scientists from the National University of Singapore and The Catholic University of Korea, now hopes to undertake clinical studies using the pH-sensitive triptolide nanogel.

The current work is detailed in ACS Nano.