pH-Sensitive Nanoformulated Triptolide as a Targeted Therapeutic Strategy for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) has one of the worst prognoses for survival as it is poorly responsive to both conventional chemotherapy and mechanism-directed therapy. This results from a lack of therapeutic concentration in the tumor tissue coupled with the highly toxic off-site effects exhibited by these compounds. Consequently, we believe the best packaging for holistic therapy for HCC will involve three components: a potent therapeutic, a rationally designed drug delivery vehicle to enrich the target site concentration of the drug, and a surface ligand that can enable a greater propensity to internalization by tumor cells compared to the parenchyma. 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.…