State Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China.
State Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China; Frontiers Science Center for Flexible Electronics (FSCFE), MIIT Key Laboratory of Flexible Electronics (KLoFE), Northwestern Polytechnical University, Xi'an 710072, China.
Acta Biomater. 2022 Oct 1;151:528-536. doi: 10.1016/j.actbio.2022.08.013. Epub 2022 Aug 13.
Phototheranostics that integrates real-time optical imaging and light-controlled therapy has recently emerged as a promising paradigm for cancer theranostics. Herein, a new small molecule dye DPP-BT-TPA with strong emission above 1000 nm and a redox-responsive prodrug camptothecin-combretastatin A4 (CPT-CA4) were designed and successfully synthesized. A multifunctional phototheranostic nanoplatform was then fabricated by encapsulating them within an amphiphilic polymer. The presence of DPP-BT-TPA enabled high-resolution imaging in the second near-infrared window (NIR-II) and efficient photothermal therapy. The prodrug was cleaved by the overexpressed glutathione (GSH) in the tumor microenvironment to release the chemotherapeutic drug CPT and the angiogenesis inhibitor CA4. Because this process can be accelerated with elevated temperature, laser-induced hyperthermia was utilized to control the drug release and enhance the therapeutic effect. Tumors in living mice were observed through NIR-II imaging after intravenous injection of the obtained nanoparticles. Improved antitumor efficacy by photothermal/chemo/antiangiogenic combination therapy was achieved with a NIR laser both in vitro and in vivo. This work provides a promising strategy for developing tumor microenvironment responsive and light-controlled theranostic platforms. STATEMENT OF SIGNIFICANCE: Fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window and near-infrared light-controlled drug release have been recognized as efficient strategies for cancer theranostics. Herein, we present a phototheranostic platform fabricated with a biocompatible NIR-II emissive dye DPP-BT-TPA and a redox-responsive prodrug camptothecin-combretastatin A4 (CPT-CA4). DPP-BT-TPA not only provides high-resolution NIR-II imaging in vivo but also enables efficient photothermal therapy. In addition, the photothermal effect largely accelerates the release of the chemotherapeutic drug CPT and the angiogenesis inhibitor CA4 in the glutathione-overexpressed tumor microenvironment. Thus, the designed phototheranostic platform can be used for NIR-II imaging-guided photothermal/chemo/antiangiogenic combination therapy for tumors with a single laser.
光热治疗将实时光学成像与光控治疗相结合，最近成为癌症治疗的一种有前途的范例。在此，设计并成功合成了一种具有强发射波长大于 1000nm 的新型小分子染料 DPP-BT-TPA 和氧化还原响应前药喜树碱-长春瑞滨（CPT-CA4）。然后，通过将它们包封在两亲聚合物内来制备多功能光热治疗纳米平台。DPP-BT-TPA 的存在使近红外二区（NIR-II）高分辨率成像和高效光热治疗成为可能。前药在肿瘤微环境中过表达的谷胱甘肽（GSH）的作用下被切割，释放出化疗药物 CPT 和血管生成抑制剂 CA4。由于这个过程可以随着温度的升高而加速，因此利用激光诱导的热疗来控制药物释放并增强治疗效果。在静脉注射获得的纳米颗粒后，通过 NIR-II 成像观察活鼠体内的肿瘤。在体外和体内，光热/化疗/抗血管生成联合治疗的抗肿瘤疗效得到了提高。这项工作为开发肿瘤微环境响应和光控治疗平台提供了一种很有前途的策略。
意义声明：在近红外二区（NIR-II，1000-1700nm）窗口进行荧光成像和近红外光控药物释放已被认为是癌症治疗的有效策略。在此，我们提出了一种由具有生物相容性的 NIR-II 发射染料 DPP-BT-TPA 和氧化还原响应前药喜树碱-长春瑞滨（CPT-CA4）制成的光热治疗平台。DPP-BT-TPA 不仅在体内提供高分辨率的 NIR-II 成像，而且还能实现高效的光热治疗。此外，光热效应大大加速了在谷胱甘肽过表达的肿瘤微环境中释放化疗药物 CPT 和血管生成抑制剂 CA4。因此，所设计的光热治疗平台可用于在单个激光下进行 NIR-II 成像引导的光热/化疗/抗血管生成联合治疗肿瘤。
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