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

摘要

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.