Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and one of the leading causes of cancer-related deaths worldwide. This may be attributed to the inefficacy of traditional cancer treatments, such as chemotherapy. Conventional medicines are not able to reach a sufficient concentration in the liver at levels not deadly to the rest of the body. In light of this obstacle, Korean and Singaporean researchers have developed a system for the targeted delivery of triptolide, a highly toxic compound, directly to HCC cells. The delivery technique employs a nanoformulated, synthesized form of triptolide, coated in an HCC-pH sensitive material. According to the study published in ACS Nano, the cancerous cells typically have a differential pH when compared to non-afflicted cells, hence the pH-sensitive coating may help to limit the exposure of the toxic triptolide only to the HCC cells in the liver.
Considering the large percentage of patients that are deemed ineligible to undergo conventional curative interventions (according to the study, this number is 30%), it is highly important to develop alternative treatment options that are able to target only the afflicted areas, without inducing toxicity in other parts of the body. Hopefully, the technique developed by the researchers will prove to be effective in addressing the treatment of those who are unable to undergo traditional treatment.
From the study in ACS Nano:
We screened a library containing hundreds of compounds against a panel of HCC cells and found the natural product, triptolide, to be more effective than sorafenib, doxorubicin, and daunorubicin, which are the current standards of therapy. However, the potential clinical application of triptolide is limited due to its poor solubility and high toxicity. Consequently, we synthesized tumor pH-sensitive nanoformulated triptolide coated with folate for use in an HCC-subpopulation that overexpresses the folate receptor. Our results show triptolide itself can prevent disease progression, but at the cost of significant toxicity. Conversely, our pH-sensitive nanoformulated triptolide facilitates uptake into the tumor, and specifically tumor cells, leading to a further increase in efficacy while mitigating systemic toxicity.