A tumor-targeting and mitochondria-anchorable probe for NIR/MRI dual-modal imaging-guided photodynamic therapy of colorectal cancer.

Phototherapy is one of the most important therapeutic modalities for tumor treatment. However, traditional phototherapy still faces huge challenges in clinical applications. Herein, we rationally designed and synthesized a tumor-targeting and mitochondria-anchorable theranostic probe, dIR-Gd, that consists of a NIR fluorophore, IR780, a cyclic peptide, cRGD, a sulfenic acid-reactive cyclohexanedione for covalent anchoring, and a MR imaging unit, DOTA-Gd3+. This probe can self-assemble into nanoparticles in an aqueous solution and shows strong MRI signals as well as an enhanced photodynamic effect. Taking advantage of its good tumor specificity and covalent immobilization within mitochondria, dIR-Gd is demonstrated to be very promising for sensitive NIR/MRI imaging and effective photodynamic therapy of αvβ3 integrin-overexpressing colorectal tumors. We believe that this covalent mitochondria-targeted probe may provide a powerful and universal tool for the accurate diagnosis and treatment of tumors.