Self-Assembled Triple-Targeted Radiosensitizer Enhances Hypoxic Tumor Targeting and Radio-Immunotherapy Efficacy.

Targeted delivery of radiosensitizers and real-time monitoring of hypoxia are crucial for overcoming radiotherapy resistance in hypoxic tumors. Here, we report A-Cy-Ni-RGD, a triple-targeted nitroimidazole (Ni)-linked radiosensitizer that self-assembles into nanoparticles (A-Cy-Ni-RGD NPs) for bimodal near-infrared fluorescence (NIR FL) and photoacoustic (PA) imaging-guided radio-immunotherapy. A-Cy-Ni-RGD NPs specifically accumulate in αβ-positive tumors, where they are hydrolyzed by carboxylesterase to form Cy-Ni-RGD NPs, with enhanced FL at 710 nm and dual PA signals at 680 and 730 nm.