Cu²⁺ Embedded Three-Dimensional Covalent Organic Framework for Multiple ROS-Based Cancer Immunotherapy.

Area of Science:

• Biomedical Engineering
• Materials Science
• Cancer Research

Background:

• Reactive oxygen species (ROS)-based cancer treatments show promise but often suffer from poor patient response due to monotypic ROS generation.
• Developing strategies to enhance the efficacy of ROS-based cancer therapies is crucial for improving patient outcomes.

Purpose of the Study:

• To develop a novel multifunctional nanomaterial for synergistic cancer immunotherapy.
• To investigate the potential of multiple ROS generation for enhanced therapeutic effects.
• To evaluate the combination therapy of the nanomaterial with an immunoblocking inhibitor for tumor inhibition.

Main Methods:

• Fabrication of a three-dimensional covalent organic framework (3D COF-TATB) embedded with copper ions (Cu²⁺) to create 3D Cu@COF-TATB.
• Utilizing porphyrins within the framework as photosensitizers for singlet oxygen (¹O₂) production and as binding sites for Cu²⁺.
• Leveraging the Fenton-like reaction of Cu⁺ (reduced from Cu²⁺ by GSH) to generate hydroxyl radicals (•OH), creating a multi-ROS system.

Main Results:

• The 3D Cu@COF-TATB system successfully generated both singlet oxygen (¹O₂) and hydroxyl radicals (•OH).
• The generated multiple ROS effectively induced immunogenic cell death (ICD) in cancer cells, enhancing immunogenicity.
• Combined treatment with 3D Cu@COF-TATB and an anti-programmed death 1 (aPD-1) immunoblocking inhibitor demonstrated significant tumor growth inhibition.

Conclusions:

• The developed 3D Cu@COF-TATB nanomaterial offers a promising synergistic strategy for multi-ROS-based cancer immunotherapy.
• This approach enhances anti-tumor immune responses by inducing ICD and can be effectively combined with immunoblocking agents.
• This work provides a valuable foundation for future multimodal cancer therapy strategies in clinical settings.