Work

Fe-MOF loaded with capmatinib to reverse immunosuppressive microenvironment and inhibit tumor metastasis after radiofrequency ablation

Year: 2025

Type: article

Abstract: Incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC) has the risk to exacerbate the tumor immunosuppressive microenvironment and promote lung metastasis. There is an urgent need to reverse the immunosuppressive microenvironment and reduce lung metastasis after iRFA. Herein, an iron-based metal-organic framework loaded with capmatinib (Fe-MOF/Cap) is employed to reverse the immunosuppressive microenvironment dominated by M2-like tumor-associated macrophages (TAMs) after iRFA and inhibit lung metastasis of HCC. On one hand, Fe-MOF/Cap repolarizes M2-like TAMs to M1-like TAMs and inhibits the expression of PD-L1 after iRFA, promoting CD8+ T cell infiltration. The infiltration of CD8+ T cells and the decrease of PD-L1 are conducive to enhance the immunotherapy after iRFA. On the other hand, Fe-MOF/Cap can inhibit lung metastasis of HCC via inhibiting the expression of c-MET. In vitro and in vivo experiments confirm that Fe-MOF/Cap is able to significantly inhibit the lung metastasis of HCC after iRFA by inhibiting the c-MET/STAT3/VEGF pathway. Fe-MOF/Cap provides a potentially promising strategy for HCC immunotherapy and anti-metastasis after iRFA, with favorable clinical prospects.

Source: Journal of Nanobiotechnology

DOI: 10.1186/s12951-025-03737-9