Radiotherapy-Driven Nanoprobes Targeting for Visualizing Tumor Infiltration Dynamics and Inducing Ferroptosis in...

Area of Science:

• Oncology
• Immunology
• Nanotechnology

Background:

• Myeloid-derived suppressor cells (MDSCs) accumulate post-radiotherapy (RT), causing immunosuppression and hindering treatment efficacy.
• Overcoming MDSC-mediated immunosuppression is crucial for improving tumor radiotherapy outcomes.

Purpose of the Study:

• To develop an anti-PD-L1 antibody-conjugated iron oxide nanoprobe (Fe3O4-αPD-L1) for targeting and inducing ferroptosis in MDSCs.
• To utilize the nanoprobe for noninvasive in vivo imaging and therapeutic intervention against RT resistance.

Main Methods:

• Conjugation of anti-PD-L1 antibody to Fe3O4 nanoparticles.
• Development of 89Zr-labeled nanoprobes for PET/MRI imaging.
• Induction of Fenton reaction and reactive oxygen species (ROS) generation within MDSCs.
• Assessment of MDSC ferroptosis, lipid peroxidation, and mitochondrial dysfunction.

Main Results:

• Fe3O4-αPD-L1 nanoprobes effectively targeted PD-L1 overexpressing MDSCs post-RT.
• Nanoprobe uptake by MDSCs led to lysosomal localization and ROS generation.
• Induced ferroptosis in MDSCs, characterized by lipid peroxidation and mitochondrial damage.
• Reprogramming of the tumor immunosuppressive microenvironment and alleviation of RT resistance.

Conclusions:

• The developed nanoprobe offers a dual modality for imaging and therapy of MDSCs.
• Targeting MDSCs via ferroptosis is a viable strategy to enhance radiotherapy efficacy.
• This approach holds potential for improving clinical outcomes in cancer patients undergoing radiotherapy.