Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
Angew Chem Int Ed Engl. 2022 Oct 4;61(40):e202209793. doi: 10.1002/anie.202209793. Epub 2022 Aug 25.
Herein, we report an activatable near-infrared (NIR) afterglow theranostic prodrug that circumvents high background noise interference caused by external light excitation. The prodrug can release hydroxycamptothecin (HCPT) in response to the high intratumoral peroxynitrite level associated with immunogenic cell death (ICD), and synchronously activate afterglow signal to monitor the drug release process and cold-to-hot tumor transformation. The prodrug itself is an ICD inducer achieved by photodynamic therapy (PDT). PDT initiates ICD and recruits first-arrived neutrophils to secrete peroxynitrite to trigger HCPT release. Intriguingly, we demonstrate that HCPT can significantly amplify PDT-mediated ICD process. The prodrug thus shows a self-sustainable ICD magnification effect by establishing an "ICD-HCPT release-amplified ICD" cycling loop. In vivo studies demonstrate that the prodrug can eradicate existing tumors and prevent further tumor recurrence through antitumor immune response.
在此，我们报告了一种可激活的近红外（NIR）余晖治疗前药，它可以规避由外部光激发引起的高背景噪声干扰。该前药可以响应与免疫原性细胞死亡（ICD）相关的高肿瘤内过氧亚硝酸盐水平释放羟基喜树碱（HCPT），并同时激活余晖信号以监测药物释放过程和冷-热肿瘤转化。前药本身是通过光动力疗法（PDT）实现的 ICD 诱导剂。PDT 引发 ICD，并募集第一批到达的中性粒细胞分泌过氧亚硝酸盐以触发 HCPT 释放。有趣的是，我们证明 HCPT 可以显著放大 PDT 介导的 ICD 过程。因此，该前药通过建立“ICD-HCPT 释放-放大 ICD”循环环，显示出自我可持续的 ICD 放大效应。体内研究表明，该前药可以通过抗肿瘤免疫反应消除现有肿瘤并防止进一步的肿瘤复发。
