癌症治疗方式逐渐从单一疗法向多模式疗法转变。研发舒缓肿瘤缺氧、特异性靶向和实时荧光追踪的协同化疗光疗系统仍然是一项挑战。 在本研究中，我们设计了一种多功能的BODIPY衍生物FBD-M，用于针对缺氧肿瘤的协同化疗光疗。FBD-M由四部分组成：1）选择作为治疗和诊断核心的BODIPY荧光团，2）修饰在中心BODIPY上携带氧气的五氟苯基，3）附着在BODIPY的一侧，用作溶酶体靶向单元以增强抗肿瘤作用的吗啉基团，以及4）引入在BODIPY的另一侧以实现化疗的芳香性亚硝基团。在将吗啉基和芳香性亚硝基引入BODIPY后，其共轭体系也扩展到实现近红外光疗。最终，通过合理设计，获得了具有近红外吸收和发射、光敏活性、缓解肿瘤缺氧的氧载体能力、高光热转化效率，良好的光稳定性、溶酶体靶向、低毒性，并具有协同化疗光疗缓解缺氧肿瘤的FBD-M。 FBD-M在体外和体内成功应用于抗癌治疗。我们的研究证明FBD-M可以作为理想的多功能治疗诊断剂。版权所有©2023 Elsevier B.V.。保留所有权利。

Cancer treatment modalities have gradually shifted from monotherapies to multimodal therapies. It is still a challenge to develop a synergistic chemo-phototherapy system with relieving tumor hypoxia, specific targeting, and real-time fluorescence tracking. In this study, we designed a multifunctional BODIPY derivative, FBD-M, for synergistic chemo-phototherapy against hypoxic tumors. FBD-M was composed of four parts: 1) The BODIPY fluorophore selected as a theranostic core, 2) A pentafluorobenzene group modified on meso-BODIPY to carry oxygen, 3) A morpholine group hooked to one side of BODIPY served as a lysosome-targeting unit for enhancing antitumor effect, and 4) An aromatic nitrogen mustard group introduced on other side of BODIPY to achieve chemotherapy. After introducing the morpholine and aromatic nitrogen mustard in BODIPY, the conjugate system of BODIPY was also expanded to realize near-infrared (NIR) phototherapy. Finally, FBD-M was obtained by a rational design, which possessed with NIR absorbance and emission, photosensitive activity, oxygen-carrying capability for relieving tumor hypoxia, high photothermal conversion efficiency, good photostability, lysosome targeting, low toxicity, and synergistic chemo-phototherapy against hypoxic tumors. FBD-M had been successfully applied for anticancer in vitro and in vivo. Our study demonstrates that FBD-M can serve as an ideal multifunctional theranostic agents.Copyright © 2023 Elsevier B.V. All rights reserved.