Cell Reports Physical Science ( IF 7.9 ) Pub Date : 2023-01-11 , DOI: 10.1016/j.xcrp.2022.101238 Guiqin Dai , Yuan Luo , Mingfeng Liao , Pengfei Zhang , Hong Pan , Ting Yin , Qianting Yang , Sirui Zheng , Jianhong Liao , Deliang Liu , Zhuojun He , Wenchang Zhao , Lijun Song , Pengfei Zhao , Lintao Cai , Zheng Zhang , Mingbin Zheng
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Latent Mycobacterium tuberculosis (Mtb) shielded in macrophages is hard to detect and eradicate, causing lethal respiratory failure and systemic inflammation. Here, we synthesize an aggregation-induced emission luminogen (AIEgen) with metabolic labeling and in situ photodynamic scavenging functions via click chemistry. By participating in cytoderm peptidoglycan biosynthesis, the wash-free AIEgen presents quick (10 min) and selective metabolic labeling to live Mtb and obtains 50-fold better detection sensitivity of tuberculosis compared with acid-fast bacilli (AFBs). Notably, the AIEgen demonstrates accurate (>96%), sensitive (>96%), and specific (100%) clinical tuberculosis diagnosis using bronchoalveolar lavage fluid (BALF) and sputum samples. Upon low-power light irradiation, the AIEgen generates lethal-dose reactive oxygen species (ROS) to break the bacterial cytoderm and significantly improves the sensitivity of Mtb to rifampicin via photodynamic ablation. The AIEgen is a clinically oriented diagnostic for tuberculosis mass screening in regions with low income and a high tuberculosis burden and shows excellent potential for photodynamic ablation of drug-resistant tuberculosis.
中文翻译:
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用于结核分枝杆菌快速检测和细胞内消融的细胞胚层代谢标记 AIEgen
隐藏在巨噬细胞中的潜伏结核分枝杆菌(Mtb) 难以检测和根除,会导致致命的呼吸衰竭和全身炎症。在这里,我们合成了具有代谢标记和原位的聚集诱导发光原 (AIEgen)通过点击化学实现光动力清除功能。通过参与细胞胚层肽聚糖的生物合成,免洗 AIEgen 可快速(10 分钟)和选择性地对活 Mtb 进行代谢标记,与抗酸杆菌 (AFB) 相比,结核病的检测灵敏度提高了 50 倍。值得注意的是,AIEgen 使用支气管肺泡灌洗液 (BALF) 和痰液样本展示了准确 (>96%)、灵敏 (>96%) 和特异性 (100%) 的临床结核病诊断。在低功率光照射下,AIEgen 产生致死剂量的活性氧 (ROS) 以破坏细菌细胞壁,并通过光动力消融显着提高 Mtb 对利福平的敏感性。