Injectable Binary-Amplified Cascade Hydrogels Suppress Post-Incomplete Microwave Ablation Relapse via Integrated...

Area of Science:

• Oncology
• Biomaterials Science
• Immunology

Background:

• Hepatocellular carcinoma (HCC) relapse post-incomplete microwave ablation (iMWA) is a significant clinical issue.
• Residual tumor cells resist death, alter fatty acid metabolism, and create an immunosuppressive microenvironment.

Purpose of the Study:

• To develop an injectable hydrogel (S/CuCo@HD) for co-delivering a CD36 inhibitor (SSO) and a copper-cobalt bimetal-organic framework (Cu-Co BMF).
• To investigate the hydrogel's potential to overcome HCC relapse by modulating metabolism and immunity.

Main Methods:

• Sustained release of SSO and Cu-Co BMF from the hydrogel post-iMWA.
• Induction of a lipid oxygen radical storm via fatty acid rewiring and metal catalysis.
• Triggering cuproptosis, mitochondrial dysfunction, and DNA damage release.
• Activating STING pathway and inducing immunogenic cell death (ICD).
• Combination therapy with anti-PD-1 treatment.

Main Results:

• The hydrogel induced a self-reinforced radical storm, leading to cell death and release of damage signals.
• These signals initiated STING activation and ICD, reprogramming the immunosuppressive microenvironment.
• The treatment promoted dendritic cell maturation, M1 macrophage polarization, and T-cell infiltration.
• Combination therapy with anti-PD-1 suppressed tumor relapse and metastasis, establishing immune memory.

Conclusions:

• The S/CuCo@HD hydrogel offers an integrated metallo-metabolic-immunomodulation strategy for HCC.
• This approach effectively suppresses tumor relapse and metastasis post-iMWA.
• The strategy shows promising translational potential for comprehensive HCC management.