Bionic Copper-Piceatannol for Polyamine Depletion-Synergized Radioimmunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Radiotherapy (RT) efficacy is limited by factors like tumor hypoxia, high glutathione levels, and immunosuppressive tumor microenvironments (ITME).
• Overcoming these challenges requires multifaceted strategies to enhance RT-induced tumor damage and immune response.

Purpose of the Study:

• To develop a novel nanoplatform (PCuP) that addresses multiple RT resistance mechanisms simultaneously.
• To evaluate the efficacy of PCuP in combination with RT for treating oral squamous cell carcinoma (OSCC) and preventing tumor recurrence.

Main Methods:

• Fabrication of a biomimetic nanoplatform (PCuP) using copper ions, piceatannol, and platelet membranes.
• In vitro and in vivo evaluation of PCuP's ability to relieve tumor hypoxia, induce immunogenic cell death (ICD), deplete polyamines, and inhibit arginase 2 (Arg2).
• Assessment of PCuP-mediated immune activation, including dendritic cell maturation and systemic antitumor immunity in OSCC models.

Main Results:

• PCuP demonstrated preferential accumulation in tumor tissues.
• PCuP effectively relieved intratumoral hypoxia by catalyzing hydrogen peroxide to oxygen.
• The nanoplatform generated reactive oxygen species (ROS) to enhance RT-induced ICD and inhibited arginase 2 (Arg2) to deplete polyamines, thereby suppressing tumor DNA repair.
• PCuP promoted dendritic cell maturation and activated systemic antitumor immunity, leading to a significant reduction in post-RT tumor recurrence in OSCC models.

Conclusions:

• The developed PCuP nanoplatform represents a novel strategy for radioimmunotherapy by integrating polyamine depletion with RT.
• This approach shows significant promise for overcoming RT resistance, enhancing antitumor immunity, and reducing tumor recurrence in OSCC.
• PCuP offers a potential new avenue for designing advanced radiosensitizers to improve clinical RT outcomes.