State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China.
Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China.
Theranostics. 2022 Sep 25;12(16):6883-6897. doi: 10.7150/thno.77457. eCollection 2022.
Immunogenic cell death (ICD)-associated immunogenicity evoked through reactive oxygen species (ROS) is an efficient way to fight against the immune-dysfunctional microenvironment, so as to provoke potent anti-tumor immunity. However, the unknown ROS dose during cancer therapies may induce adverse immune responses (e.g., insufficient ICD, toxicity toward normal tissues or immune system). Herein, we developed a pyrido pyrazine - thiophene based semiconducting polymer as novel near-infrared (NIR) organic afterglow nanoparticles for the real-time visualization of self-generated ROS, during photodynamic-mediated immunogenic cell death. Specifically, we introduced the strong "acceptor" (pyrido pyrazine) into thiophene based semiconducting polymer to redshift emission wavelength, and further modulate the "donor" to afford more afterglow reaction sites and reducing ΔEst, so as to enhance luminescence intensity. The semiconducting polymer-based afterglow nanoparticles exhibit strong afterglow emission with longer-wavelength emission (> 800 nm), compared with the reported organic afterglow nanoparticles (e.g., MEHPPV, PFODBT or Chlorin, < 690 nm), which endows this afterglow nanoparticles with a greatly improvement of signal to noise ratio. Moreover, the photodynamic effect of this afterglow nanoparticles can induce immunogenic cell death of cancer cells and further cause immune responses in mice. The NIR afterglow signal presents a good relationship with ROS generation, immunogenic cell death and outcome of treatment. Therefore, it was able to provide a non-invasive tool for predicting the degree of ICD that occurs during ROS-mediated cancer therapy and may contribute to precise immunotherapy.
免疫原性细胞死亡（ICD）相关的免疫原性通过活性氧（ROS）诱发，是对抗免疫功能障碍微环境的有效方法，从而引发有效的抗肿瘤免疫。然而，癌症治疗过程中ROS 剂量的未知可能会诱导不良免疫反应（例如，ICD 不足、对正常组织或免疫系统的毒性）。 在此，我们开发了一种基于吡啶并吡嗪-噻吩的半导体聚合物作为新型近红外（NIR）有机余晖纳米粒子，用于在光动力介导的免疫原性细胞死亡过程中实时可视化自产生的 ROS。具体而言，我们将强“受体”（吡啶并吡嗪）引入基于噻吩的半导体聚合物中以红移发射波长，并进一步调节“供体”以提供更多的余晖反应位点并降低 ΔEst，从而增强发光强度。 与报道的有机余晖纳米粒子（例如 MEHPPV、PFODBT 或 Chlorin，<690nm）相比，基于半导体聚合物的余晖纳米粒子具有更强的余晖发射，发射波长更长（>800nm），这使这些余晖纳米粒子的信噪比大大提高。此外，该余晖纳米粒子的光动力效应可以诱导癌细胞的免疫原性细胞死亡，并进一步在小鼠中引起免疫反应。 NIR 余晖信号与 ROS 生成、免疫原性细胞死亡和治疗效果之间存在良好的关系。因此，它能够为预测 ROS 介导的癌症治疗过程中发生的 ICD 程度提供一种非侵入性工具，并可能有助于精确的免疫治疗。
