Tailored Liposomal Nanomedicine Suppresses Incomplete Radiofrequency Ablation-Induced Tumor Relapse by Reprogramming...

Area of Science:

• Oncology
• Nanomedicine
• Immunotherapy

Background:

• Radiofrequency ablation (RFA) is effective for small hepatocellular carcinoma (HCC) but limited for advanced stages due to incomplete ablation (iRFA).
• iRFA in HCC promotes tumor immunosuppression, increased pyruvate kinase M2 (PKM2) expression, and poor prognosis.
• Existing treatments struggle with large, multiple, or irregular HCC tumors post-RFA.

Purpose of the Study:

• To develop a multifunctional nanomedicine to overcome iRFA-induced treatment failure in advanced HCC.
• To investigate the nanomedicine's ability to reprogram the tumor microenvironment and enhance anti-tumor immunity.
• To evaluate the synergistic therapeutic effect of the nanomedicine combined with iRFA.

Main Methods:

• Fabrication of a multifunctional nanomedicine encapsulating shikonin (PKM2 inhibitor), anti-PD-L1, and spermidine within lipid bilayers (liposomal SPS-NPs).
• In vitro and in vivo studies to assess the nanomedicine's effect on cancer cell glycolysis, immune cell function, and tumor growth.
• Combination therapy evaluating iRFA with intravenous liposomal SPS-NPs injection.

Main Results:

• The nanomedicine effectively inhibited cancer cell glycolysis by targeting PKM2.
• Liposomal SPS-NPs reprogrammed tumor-infiltrating lymphocytes and reversed immunosuppression.
• Combined therapy demonstrated potent anti-tumor immunity, suppressing residual tumor growth and lung metastasis.

Conclusions:

• The developed liposomal nanomedicine shows promise in reversing iRFA-induced immunosuppression in advanced HCC.
• This approach potentiates RFA therapeutic benefits by reprogramming the tumor microenvironment.
• The nanomedicine offers a potential strategy for improving outcomes in advanced HCC patients.