Highly Inoxidizable Heptamethine Cyanine–Glucose Oxidase Conjugate Nanoagent for Combination of Enhanced Photothermal Therapy and Tumor Starvation

Abstract Heptamethine cyanine dye (Cy7) has been widely applied in cell imaging and tumor phototherapy by virtue of its excellent photophysical properties and biocompatibility. However, in the presence of oxygen, large conjugated skeletons are easily destroyed by photooxidation reaction under light irradiation, which greatly limits its inoxidizability and photothermal therapy (PTT) effect. Accordingly, in this study, a new strategy (Cy‐GOx) is developed by the catalytic reaction of glucose oxidase (GOx) that consumes oxygen to highly improve the antioxidant capacity of Cy7, achieving the combination of enhanced PTT and starvation therapy. During this catalytic reaction, glucose as an important nutrient for cancer cell growth is consumed, achieving GOx‐mediated tumor starvation therapy. The fluorescence and intersystem crossing (ISC) of Cy‐GOx are greatly inhibited, which ensures that the absorbed photon energy is mainly released by means of nonradiative transition, significantly improving its photothermal effect. Of note, this strategy can effectively realize tumor inhibition by both intratumoral injection and intravenous injection. Thus, it is believed that this design concept will provide a new strategy for improving the antioxidant capacity and photothermal effect of Cy7 in combination therapy for enhanced antitumor efficacy.