Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, P. R. China.
College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, P. R. China.
Adv Mater. 2021 Oct;33(41):e2103748. doi: 10.1002/adma.202103748. Epub 2021 Aug 22.
The development of multifunctional nanoplatforms has been recognized as a promising strategy for potent photodynamic theranostics. Aggregation-induced emission (AIE) photosensitizers undergoing Type-I reactive oxygen species (ROS) generation pathway appear as potential candidates due to their capability of hypoxia-tolerance, efficient ROS production, and fluorescence imaging navigation. To further improve their performance, a facile and universal method of constructing a type of glutathione (GSH)-depleting and near-infrared (NIR)-regulated nanoplatform for dual-modal imaging-guided photodynamic therapy (PDT) is presented. The nanoplatforms are obtained through the coprecipitation process involving upconversion nanoparticles (UCNPs) and AIE-active photosensitizers, followed by in situ generation of MnO as the outer shell. The introduction of UCNPs actualizes the NIR-activation of AIE-active photosensitizers to produce ·OH as a Type-I ROS. Intracellular upregulated GSH-responsive decomposition of the MnO shell to Mn realizes GSH-depletion, which is a distinctive approach for elevating intracellular ·OH. Meanwhile, the generated Mn can implement T -weighted magnetic resonance imaging (MRI) in specific tumor sites, and mediate the conversion of intracellular H O to ·OH. These outputs reveal a triple-jump ·OH production, and this approach brings about distinguished performance in FLI-MRI-guided PDT with high-efficacy, which presents great potential for future clinical translations.
多功能纳米平台的发展已被认为是一种有前途的强光动力治疗策略。由于具有耐缺氧能力、高效产生活性氧（ROS）和荧光成像导航的能力，基于聚集诱导发光（AIE）的光敏剂呈现为潜在的候选物，采用Ⅰ型 ROS 生成途径。为了进一步提高其性能，提出了一种简便通用的方法，用于构建一种用于双模式成像引导光动力治疗（PDT）的谷胱甘肽（GSH）耗竭和近红外（NIR）调控的纳米平台。该纳米平台是通过包含上转换纳米粒子（UCNPs）和 AIE 活性光敏剂的共沉淀过程获得的，然后原位生成 MnO 作为外壳。UCNPs 的引入实现了 AIE 活性光敏剂的 NIR 激活，以产生作为Ⅰ型 ROS 的·OH。细胞内上调的 GSH 响应性 MnO 壳的分解为 Mn 实现了 GSH 耗竭，这是提高细胞内·OH 的独特方法。同时，生成的 Mn 可以在特定的肿瘤部位实现 T 加权磁共振成像（MRI），并介导细胞内 H 2 O 转化为·OH。这些结果揭示了三重跳跃·OH 的产生，这种方法在 FLI-MRI 引导的 PDT 中具有高效的性能，为未来的临床转化带来了巨大的潜力。
