June 20, 2024

Enhanced Treatment for Liver Carcinoma with Drug-Eluting Hydrogel Developed by Terasaki Institute

A team of scientists from the Terasaki Institute for Biomedical Innovation (TIBI) has developed an innovative drug-eluting hydrogel that shows promise in the treatment of hepatocellular carcinoma (HCC), a deadly form of liver cancer. According to their recent publication in Advanced Functional Materials, this hydrogel can deliver drugs in a sustained manner and has the ability to promote anti-tumor immune responses. These properties inhibit tumor cell proliferation and growth, providing a more effective method for inducing tumor cell death.

HCC is a leading cause of cancer-related deaths worldwide, with an estimated one million new cases expected to be diagnosed by 2025. Although treatment options exist, they often fall short of providing long-term remission. Small liver tumors can be surgically removed if detected at an early stage, but the recurrence rate in these patients is alarmingly high at 70%. Liver transplantation is another viable option, but there is a severe shortage of suitable liver donors, and successful outcomes are mainly observed in cases diagnosed early on.

One commonly used treatment method is trans-arterial chemoembolization (TACE), in which tiny microbead particles are delivered via a catheter into an artery supplying blood and nutrients to the tumor. These particles block the blood flow to the tumor, restricting its growth. Additionally, the particles can serve as vehicles for delivering anti-cancer drugs directly to the tumor cells, while the restricted blood flow concentrates the drug in the tumor region.

Although TACE offers a more targeted and safer approach compared to earlier systemic chemotherapeutic methods, it is not without limitations. Bead dispersion is often uneven, as the beads can break apart or aggregate, hindering deep penetration into the tumors. Furthermore, delivering chemotherapeutic drugs to the tumor site alone may not be sufficient to eradicate malignant tumor growth. These tumors exhibit unrestricted growth due to their ability to suppress the body’s natural immune response. Immunotherapeutic drugs can reverse this suppression and reinstate the body’s immune defenses, destroying tumor cells and inhibiting further growth.

Given the ability of the chemotherapeutic agent doxorubicin (DOX) to prime tumor cells for immunogenic cell death, researchers at TIBI aimed to develop a drug delivery system that could sequentially deliver both DOX and the immunotherapeutic drug anti-PD-1 in a targeted, sustained, and controllable manner. Through in vitro optimization experiments, the team formulated a gelatin hydrogel containing Laponite nanoclay. This hydrogel not only improves injectability but also enables pH-controlled drug delivery.

Subsequent in vitro experiments helped identify the optimal formulation and pH conditions for the release of both DOX and anti-PD-1 by the hydrogel. The team also established that DOX release by the hydrogel effectively primes anti-tumor immune responses at the tumor site.

To test the efficacy of this drug delivery hydrogel platform, in vivo experiments were conducted using mouse models injected with liver tumor cells. The mice received treatments with both dual-loaded hydrogels containing DOX and anti-PD-1, as well as singly loaded hydrogels containing only DOX. The mice were monitored for tumor size and survival time, revealing that those treated with the combination hydrogels had the longest survival times and the smallest tumor sizes.

Further tests showed that the combination drug-loaded hydrogels demonstrated the highest infiltration by anti-tumor immune cells, the greatest reduction in tumor cell proliferation, and the highest level of tumor cell death.

Dr. Ali Khademhosseini, the Director and CEO of TIBI, stated that the combination of chemotherapeutic and immunotherapeutic drug deliveries significantly enhances the anti-tumor efficacy against hepatocellular carcinoma. This innovative approach improves current treatment methods and offers renewed hope for patients facing this deadly disease.

In conclusion, the development of the drug-eluting hydrogel by Terasaki Institute represents a significant advancement in the treatment of hepatocellular carcinoma. By providing sustained drug delivery and promoting anti-tumor immune responses, this hydrogel shows potential in inhibiting tumor growth and inducing tumor cell death. Further research and clinical trials are necessary to validate its effectiveness in human patients and to explore its potential as a viable treatment option for HCC.

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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it