癌症严重影响患者的生活质量。协同化疗和光热疗法（PTT）已成为一种有前景的抗癌范例，可以在达到预期的治疗效果的同时减轻副作用。然而，化疗/PTT联合治疗受到了穿透深度有限、肿瘤细胞对热的抵抗能力以及药物生物可用性低的困扰。在这里，我们开发了多功能纳米颗粒（BTP/DOX/2DG NPs），共载有近红外区域II（NIR-II）光激发给受体给受体（D-A-D）小分子、多柔比星（DOX）和2-脱氧-D-葡萄糖（2-DG），用于加强饥饿/化疗/NIR-II PTT联合治疗。我们合成了苯硼酸（PBA）修饰的水溶性D-A-D分子（BBT-TF-PBA），不仅通过给受体配位相互作用PBA-二醇键高度结合DOX和2-DG，而且还可以作为NIR-II荧光成像、NIR-II光声成像和NIR-II PTT的光活性剂。在肿瘤微环境的酸性和氧化条件下，给受体配位相互作用和PBA-二醇键分解，同时释放出DOX和2-DG从BTP/DOX/2DG NPs以实现有效的化疗和饥饿疗法。2-DG还能有效抑制热休克蛋白的表达，进一步增强NIR-II PTT和化疗效果。体外和体内实验证明了BTP/DOX/2DG NPs在化疗、NIR-II PTT和饥饿疗法中的联合作用。本文受版权保护。保留所有权利。

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.This article is protected by copyright. All rights reserved.