Red Blood Cell-Mimic Nanocatalyst Triggering Radical Storm to Augment Cancer Immunotherapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Oncology

Background:

• Red blood cells (RBCs) show potential in cancer therapy by targeting tumor hypoxia and inducing oxidative damage.
• Current limitations include insufficient oxygen transport and reactive oxygen species (ROS) generation rates in tumor tissues.
• Artificial RBCs (aRBCs) offer a promising platform to overcome these limitations.

Purpose of the Study:

• To develop novel artificial RBCs (FTP@RBCM) with enhanced ROS generation for oncotherapy.
• To investigate the multidimensional catalytic activities of Fe-protoporphyrin-based hybrid metal-organic frameworks (FTPs) within the aRBC system.
• To evaluate the therapeutic efficacy of FTP@RBCM in combination with immune checkpoint blockade for synergistic cancer treatment.

Main Methods:

• Fabrication of FTP@RBCM by coating FTP cores with RBC membranes (RBCMs).
• Assessment of FTP@RBCM's catalytic activities, including photodynamic/chemodynamic-like, catalase-like, and glutathione peroxidase-like functions.
• In vivo evaluation of FTP@RBCM's tumor accumulation, therapeutic efficiency, and immune response induction, including combination therapy with T cell immunoglobulin and mucin-containing molecule 3 (Tim-3) blockade.

Main Results:

• FTP@RBCM demonstrated multidimensional catalytic activities, leading to radical storm production.
• RBCM coating facilitated enhanced tumor accumulation and therapeutic efficiency of FTP@RBCM.
• ROS-mediated therapy induced local inflammation and immunogenic cancer cell death, triggering a systemic antitumor immune response.
• Combination therapy with Tim-3 blockade resulted in primary tumor elimination and abscopal effects on distant tumors.

Conclusions:

• FTP@RBCM exhibits potent ROS-mediated oncotherapy via multidimensional catalytic pathways.
• The RBC-mimicking nanocatalyst design enhances tumor targeting and therapeutic outcomes.
• Synergistic treatment combining FTP@RBCM with immune checkpoint blockade offers a promising strategy for comprehensive cancer treatment, including abscopal effects.