Injectable Thermal-Protective Hydrogel Enables Curative Tumor Ablation via Chemo-Immunomodulation

Area of Science:

• Biomaterials Science
• Cancer Therapy
• Immunomodulation

Background:

• Image-guided thermal ablation is limited by insufficient tumor destruction and thermal damage to surrounding tissues.
• Sublethal heat at ablation margins can create an immunosuppressive tumor microenvironment, increasing recurrence risk.

Purpose of the Study:

• To develop an injectable hydrogel (MR@CaP@HA) for in situ thermal insulation and dual-responsive (pH/GSH) chemo-immunomodulatory drug delivery.
• To overcome thermal safety and immune resistance barriers in thermal ablation therapies.

Main Methods:

• Development of MR@CaP@HA hydrogel with thermal insulation properties.
• Utilizing a disulfide-cross-linked hyaluronic acid network for glutathione (GSH)-dependent drug release.
• Dual-responsive (pH/GSH) delivery of mitoxantrone (MIT) and resiquimod (R848) via MR@CaP nanoparticles.

Main Results:

• MR@CaP@HA hydrogel provided 5-10 mm thermal insulation, maintaining surrounding tissues below 45 °C during ablation.
• The system induced robust immunogenic cell death, dendritic cell maturation, and high M1 macrophage polarization (95% in vitro, 35% in vivo).
• Integrated therapy achieved complete tumor eradication in 50% of animals, sterilizing residual tumor cells.

Conclusions:

• The developed material-driven platform enhances thermal ablation safety and efficacy.
• Coordinated thermal modulation and programmable drug release overcome key limitations in current ablation techniques.
• This strategy offers a translational approach for improved cancer treatment outcomes.