A Simple Small Molecule with Synergistic Passive and Active Dual-Targeting Effects for Imaging-Guided Photothermal Cancer Therapy.

Photothermal therapy allows spatiotemporal control of the treatment effect only at the site of the disease and provides promising opportunities for imaging-guided precision therapy. However, the development of photothermal transduction agents (PTAs) for tumor-specific accumulation and precision imaging, avoiding toxicity to the surrounding healthy tissue, is still challenging. Herein, a cyclooxygenase-2-specific small-organic-molecule-based PTA (Cy7-TCF-IMC) is developed, which can self-assemble into nanosaucers having unique photothermal and photoacoustic properties. Specifically, the self-assembling nature of Cy7-TCF-IMC affords preferential accumulation in tumors arising from synergistic passive enhanced permeability and retention effects and active targeting for precision theranostics. Antitumor therapy results show that these Cy7-TCF-IMC nanosaucers are highly photoacoustic imaging-guided PTAs for tumor ablation. These findings suggest the self-assembled Cy7-TCF-IMC nanosaucer represents a new paradigm as a single-component supramolecular medicine that can synergistically optimize passive and active targeting, thereby improving the therapeutic index of cancer and future clinical outcomes.