Novel Drug-Delivery Platform Enhances Efficacy of Liver Cancer Treatment

Multilayer hydrogel cubes provide a potential solution for the poor solubility and low bioavailability of an anti-cancer drug.

Hydrogel cubes loaded with a potent anticancer drug could be the next treatment option for liver cancer.

In a study published in Acta Biomaterialia, investigators developed microcubes that can be loaded with a hydrophobic anti-cancer drugs and delivered directly to the cancer cells. The authors hope the delivery system will improve the efficacy of anti-cancer drugs and reduce adverse events.

“We believe that our novel drug-delivery platform for the highly potent anti-cancer drug BA-TPQ provides a facile method for encapsulation of hydrophobic drugs and can facilitate enhanced efficacy for liver cancer therapy,” the authors wrote.

The 2-micrometer cubes consist of several layers of cross-linked poly(methacrylic acid) formed on a porous scaffold that is then removed. According to the authors, poly(methacrylic acid) is both non-toxic and biocompatible for clinical use.

BA-TPQ is one of the most potent analogs of natural anti-cancer compounds from the Philippine sponge Zyzzya fuliginosa. It has the potential to effectively fight against breast and prostate cancer lines, but its poor solubility, low bioavailability, and toxic effects has prevented its implementation.

Although the BA-TPQ-hydrogel cubes are soft, they can retain their cubic shape to aid in the uptake of cancer cells—–even after being freeze-dried and then resuspended in solution. Higher redox potential facilitates dissolution of the microcubes and release of the BA-TPQ drug. Often, cancer cells have higher redox potential than normal cells, the authors noted.

Using 2 lines of liver cancer cells compared with normal liver cells, the investigators found that the anticancer BA-TPQ-hydrogel platform retains the selective activity of BA-TPQ to hepatocellular carcinoma cells. They also discovered that the drug-loaded microcubes had an impact on the expression of genes involved in cancer growth or prevention.

“Encapsulating BA-TPQ in the hydrogels amplifies the potency of the drug via down-regulation of MDM2 oncogenic protein and upregulation of p53 (a tumor suppressor) and p21 (cell proliferation suppressor) expression in HepG2 liver cancer cells,” the author wrote. “Moreover, enhanced inhibition of MDM2 protein expression by BA-TPQ-hydrogel cubes is independent of p53 status in Huh7 cells.”

The findings suggest that the BA-TPQ-hydrogel cubes may be a successful candidate for anti-tumor treatment in cancer cells with p53 mutation.

“Many potent anticancer drugs are hydrophobic and lack tumor selectivity, which limits their application in cancer therapy,” the authors wrote. “In this study, we provide a facile method to prepare a multilayer hydrogel-based platform with controlled nanostructure, cubical shape, and redox-responsiveness for delivery of highly potent anticancer therapeutics, hydrophobic BA-TPQ.

“Overall, the produced BA-TPQ-hydrogel cubes demonstrate a high potential for clinical liver cancer therapy.”