A Tumor Targeting Strategy of Phytoflavonoid Biochanin A for Efficient Fluorescence-Guided Chemotherapy.

Cancer chemotherapy using natural phytochemicals, especially including isoflavone biochanin A (BCA), has attracted considerable attention because of the potent antitumor therapeutic effect and excellent biosafety. However, the preclinical application of BCA is still generally limited by its poor water solubility and low biological availability. To overcome these important limitations, a tumor targetable hemicyanine-based near-infrared (NIR) theranostic agent is rationally designed and prepared to improve the water solubility, tumor targetability, and antitumor activity of BCA. A key point to enhance the tumor targeting efficiency of BCA is the combination of a tumor-targeted water-soluble zwitterionic NIR fluorophore (ZW800-Cl) and BCA to create the hemicyanine structure, named BCA-ZW. Owing to the long-wavelength emission (>750 nm) and large Stokes shift (72 nm) of BCA-ZW, the in vivo performance of BCA-ZW is effectively monitored. The molecularly engineered BCA-ZW not only exhibits high targeting ability to HT-29 xenograft tumors but also induces high levels of reactive oxygen species (ROS) generation in the tumor tissues. Therefore, the fluorescence-guided chemotherapy by BCA-ZW to the tumor-bearing mouse model achieves the enhanced antitumor effect of BCA. This work provides a simple but effective strategy to design NIR fluorescent phytoflavonoids as potential therapeutic agents for further biomedical applications.