School of Engineering, China Pharmaceutical University, Nanjing 211198, China.
School of Engineering, China Pharmaceutical University, Nanjing 211198, China.
Acta Biomater. 2024 Oct 15;188:315-328. doi: 10.1016/j.actbio.2024.09.001. Epub 2024 Sep 5.
Photodynamic therapy (PDT) has attracted widespread attention from researchers as an emerging cancer treatment method. There have been many reports on various types of NIR-II photosensitizers for imaging and treatment of tumor sites. However, there are few reports on the development of NIR-II organic small molecule photosensitizers that have intelligent response to the tumor microenvironment, precise imaging, real-time treatment, and high biocompatibility. In this work, we developed a series of NIR-II photosensitizers (RBTs) with near-infrared excitation, good photostability, and large Stokes shift. Among them, RBT-Br exhibited higher reactive oxygen species (ROS) generation efficiency due to the introduction of halogen heavy atoms to enhance intersystem crossing (ISC). It is noteworthy that RBT-Br can generate singlet oxygen (O) and superoxide anion radicals (O) simultaneously under 730 nm laser. Subsequently, we used molecular engineering technology to construct three pH-responsive NIR-II photosensitizers (RBT-pHs) by utilizing the closure of the lactam ring, among which RBT-pH-1 (pK = 6.78) is able to be directionally activated under the stimulation of tumor micro-acid environment, with its fluorescence emission window reaching 933 nm. Subsequently, RBT-pH-1 NPs encapsulated in DSPE-mPEG were applied for PDT treatment of mouse tumors. The results showed that RBT-pH-1 NPs were activated by the acidic tumor microenvironment and generated ROS under laser excitation, exhibiting precise tumor imaging and significant tumor growth inhibition. We look forward to these multifunctional NIR-II organic small molecule photosensitizers providing a more efficient approach for clinical treatment of tumors. STATEMENT OF SIGNIFICANCE: A reversible pH-switchable NIR-II nano-photosensitizer RBT-pH-1 NPs (pK = 6.76) is developed for precise imaging and PDT therapy of mouse tumors, which can be effectively used for targeted enrichment and activation of tumor micro-acid environments. The results show that this NIR-II photosensitizer generates ROS through tumor micro-acid environment stimulation and laser triggering, showing precise tumor imaging guidance and significant tumor growth inhibition.
光动力疗法（PDT）作为一种新兴的癌症治疗方法，引起了研究人员的广泛关注。已经有许多关于各种类型的近红外二区（NIR-II）光动力治疗剂用于肿瘤部位成像和治疗的报道。然而，开发对肿瘤微环境具有智能响应、精确成像、实时治疗和高生物相容性的 NIR-II 有机小分子光动力治疗剂的报道很少。在这项工作中，我们开发了一系列具有近红外激发、良好光稳定性和大斯托克斯位移的 NIR-II 光动力治疗剂（RBTs）。其中，RBT-Br 由于引入了卤族重原子来增强系间窜跃（ISC），表现出更高的活性氧（ROS）生成效率。值得注意的是，RBT-Br 可以在 730nm 激光下同时产生单线态氧（1O2）和超氧阴离子自由基（O2-）。随后，我们利用分子工程技术，通过利用内酰胺环的闭合，构建了三种 pH 响应型 NIR-II 光动力治疗剂（RBT-pHs），其中 RBT-pH-1（pK = 6.78）能够在肿瘤微酸环境的刺激下定向激活，其荧光发射窗口达到 933nm。随后，将包封在 DSPE-mPEG 中的 RBT-pH-1 NPs 用于小鼠肿瘤的 PDT 治疗。结果表明，RBT-pH-1 NPs 在酸性肿瘤微环境的刺激下被激活，并在激光激发下产生 ROS，表现出精确的肿瘤成像和显著的肿瘤生长抑制。我们期待这些多功能 NIR-II 有机小分子光动力治疗剂为肿瘤的临床治疗提供更有效的方法。
开发了一种可逆的 pH 开关近红外二区纳米光动力治疗剂 RBT-pH-1 NPs（pK = 6.76），用于小鼠肿瘤的精确成像和 PDT 治疗，可有效用于肿瘤微酸环境的靶向富集和激活。结果表明，这种近红外二区光动力治疗剂通过肿瘤微酸环境刺激和激光触发产生 ROS，表现出精确的肿瘤成像指导和显著的肿瘤生长抑制。
