Microwave ablation (MWA) serves as a vital clinical tool for treating hepatocellular carcinoma (HCC). However, the accumulation of lactate following MWA often promotes tumor recurrence and metastasis. To overcome this, researchers developed a dual-transformable MgGa-MOF nanoplatform designed for HCC lactate metabolism blockade and immune reactivation. This innovative strategy effectively converts metabolic fuel into a cellular burden, suppressing both primary and metastatic tumor growth.

Mechanisms of HCC Lactate Metabolism Blockade

The nanoplatform, known as DMGTF NCs, utilizes a dual-transformation approach to reshape the tumor microenvironment. Specifically, microwave irradiation triggers the release of diclofenac sodium from the nanostructure. This drug effectively inhibits MCT4-mediated lactate efflux, leading to intracellular lactate accumulation and energy disruption. Furthermore, the bimetallic framework generates reactive oxygen species (ROS) under microwave activation. These ROS impair mitochondrial oxidation, which further intensifies metabolic stress within the cancer cells. Consequently, this multi-pronged HCC lactate metabolism blockade prevents residual tumor cells from using lactate as fuel.

Boosting Immune Reactivation and Antitumor Power

In addition to metabolic targeting, the nanoplatform enhances the body's immune response against cancer. Specifically, the framework-derived Mg²⁺ ions restart T-cell activity and boost their proliferation. These ions also augment the secretion of IFN-γ, which transforms an immunosuppressive environment into a potent antitumor landscape. Therefore, the combination of metabolic stress and immune reactivation provides a robust defense against post-ablation relapse. This strategy offers promising insights into improving long-term outcomes for liver cancer patients undergoing interventional therapies.

What is the impact of lactate accumulation on HCC treatment?

Lactate acts as a metabolic fuel for surviving cancer cells and creates an acidic environment that suppresses the immune system, leading to higher rates of tumor recurrence after ablation.

How does the DMGTF nanoplatform target liver cancer?

It uses folic acid for targeting and microwave energy to release diclofenac, which blocks lactate efflux, while simultaneously generating ROS to disrupt internal cancer metabolism and releasing Mg²⁺ to activate T-cells.

Disclaimer: This content is for informational and educational purposes only. It does not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

1. Li Y et al. A dual-transformable MgGa-MOF nanoplatform for HCC therapy via lactate metabolism blockade and immune reactivation. J Nanobiotechnology. 2026 Apr 05. doi: 10.1186/s12951-026-04356-8. PMID: 41937209.


2. Zhang Q et al. Monocarboxylate transporter 4 inhibition potentiates hepatocellular carcinoma immunotherapy through enhancing T cell infiltration and immune attack. Hepatology. 2023;77(1):109-123.


3. Gottfried E et al. New Aspects of an Old Drug – Diclofenac Targets MYC and Glucose Metabolism in Tumor Cells. PLoS ONE. 2013;8(7):e66987.