Phenylboronic Acid-Modified Near-Infrared Region Ii Excitation Donor–Acceptor–Donor Molecule for 2-Deoxy-D-Glucose Improved Starvation/Chemo/Photothermal Combination Therapy

Cancer seriously affects the quality of life of patients with the disease. Synergistic chemotherapy and photothermal therapy (PTT) have emerged as a promising anticancer paradigm to achieve expected therapeutic effects while mitigating side effects. However, the chemo/PTT combination therapy suffers from limited penetration depth, thermo-resistance performance of tumor cells, and low drug bioavailability. Herein, we developed multifunctional nanoparticles (BTP/DOX/2DG NPs) coloaded with near-infrared region II (NIR-II) light excitation donor–acceptor–donor (D-A-D) small molecules, doxorubicin (DOX), and 2-deoxy-D-glucose (2-DG) for reinforced starvation/chemo/NIR-II PTT combination therapy. Our synthesized phenylboronic acid (PBA)-modified water-soluble D-A-D molecule (BBT-TF-PBA) not only exhibits high binding ability to DOX and 2-DG through donor–acceptor coordination interactions PBA-diol bonds but also serve as a photoactive agent for NIR-II fluorescence imaging, NIR-II photoacoustic imaging, and NIR-II PTT. Under the acidic and oxidizing conditions in the tumor microenvironment, donor–acceptor coordination interactions and PBA-diol bond are decomposed, simultaneously releasing DOX and 2-DG from BTP/DOX/2DG NPs to achieve effective chemotherapy and starvation therapy. 2-DG also effectively inhibits the expression of heat shock protein and further enhances NIR-II PTT and chemotherapy efficiency. In vitro and in vivo experiments demonstrated the combination effect of BTP/DOX/2DG NPs for chemotherapy, NIR-II PTT, and starvation therapy. This article is protected by copyright. All rights reserved