XOR-mediated tumor-selective nanomaterial therapy: achieving tumor and immune cell dual regulation through...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunotherapy

Background:

• High reactive oxygen species (ROS) concentration has dual roles in cancer, potentially inducing tumor cell death and promoting antitumor immune responses.
• Targeting ROS effectively at tumor sites remains a challenge for sustained therapeutic efficacy.

Purpose of the Study:

• To synthesize and evaluate a novel nanoplatform, ZIF-8@XOR, for enhanced ROS generation and targeted cancer therapy.
• To investigate the potential of ZIF-8@XOR in inducing tumor cell death and stimulating antitumor immunity.

Main Methods:

• Synthesis of ZIF-8@XOR nanoplatform combining Xanthine oxidoreductase (XOR) and Zeolite imidazolate framework-8 (ZIF-8).
• In vitro and in vivo evaluation of ZIF-8@XOR for ROS generation, tumor cell targeting, and induction of apoptosis.
• Assessment of macrophage polarization and immune cell infiltration in the tumor microenvironment.

Main Results:

• ZIF-8@XOR effectively targets tumor cells and generates intracellular ROS, leading to tumor cell death both in vitro and in vivo.
• Intracellular ROS generation promotes M1-type macrophage polarization and enhances the tumor-associated antigen pool.
• Increased infiltration and activation of macrophages and CD8+ T cells were observed, indicating a robust adaptive anti-tumor immune response.

Conclusions:

• The developed ZIF-8@XOR nanomaterial shows significant potential as a novel therapeutic tool for gastric cancer immunotherapy.
• The nanoplatform effectively leverages ROS to bridge innate and adaptive immunity against tumors.