GSH-Responsive Radiosensitizers with Deep Penetration Ability for Multimodal Imaging-Guided Synergistic Radio-Chemodynamic Cancer Therapy

Radiotherapy (RT) utilizes the non-invasive and high penetration X-ray as the energy source to eliminate deep-seated tumors. The efficacy of RT can be optimized by designing effective radiosensitizers and synergizing with other treatment methods. Glutathione (GSH)-responsive radio-sensitizing nanovesicles are designed with size-transformability via self-assembly of gold-manganese oxide Janus nanoparticles (JNPs) encapsulating the near-infrared fluorescence (NIR) dye (IR1061). In the presence of GSH, JNP vesicles (Ves) dissociate into smaller gold (Au) NPs and manganese ion (Mn2+) that not only penetrate into the deeper layers of the tumor but also deplete the GSH and trigger chemodynamic therapy (CDT) through a Fenton-like reaction, which augments the efficacy of RT. In addition, the IR1061 released from the disintegrated nanostructures fluoresces in the NIR-II window, and along with photoacoustic (PA) and magnetic resonance imaging (MRI) enables high precision tumor detection. The combination of JNP Ve and X-ray irradiation achieves multimodal image-guided ablation of subcutaneous as well as deep-seated tumors in murine models. Therefore, this novel multimodal image-guided RT/CDT therapeutic platform is a promising strategy in high-precision tumor therapy.

Automated summary

Radiotherapy using X-rays is effective in treating deep-seated tumors, and can be optimized by designing sensitizing nanovesicles. These nanovesicles release gold and manganese ions in the presence of GSH, triggering chemodynamic therapy and enhancing the efficacy of radiotherapy by penetrating deeper into the tumor layers.