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光点击反应构建用于抗结核的谷胱甘肽响应型诊疗系统。

Photoclick Reaction Constructs Glutathione-Responsive Theranostic System for Anti-Tuberculosis.

作者信息

Zheng Judun, Long Xun, Chen Hao, Ji Zhisheng, Shu Bowen, Yue Rui, Liao Yechun, Ma Shengchao, Qiao Kun, Liu Ying, Liao Yuhui

机构信息

Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, China.

Department of Science and Education, The Third People's Hospital of Bijie City, Bijie, China.

出版信息

Front Mol Biosci. 2022 Feb 14;9:845179. doi: 10.3389/fmolb.2022.845179. eCollection 2022.

Abstract

Tuberculosis (TB) is a virulent form of an infectious disease that causes a global burden due to its high infectivity and fatality rate, especially the irrepressible threats of latent infection. Constructing an efficient strategy for the prevention and control of TB is of great significance. Fortunately, we found that granulomas are endowed with higher reducibility levels possibly caused by internal inflammation and a relatively enclosed microenvironment. Therefore, we developed the first targeted glutathione- (GSH-) responsive theranostic system (RIF@Cy5.5-HA-NG) for tuberculosis with a rifampicin- (RIF-) loaded near-infrared emission carrier, which was constructed by photoclick reaction-actuated hydrophobic-hydrophobic interaction, enabling the early diagnosis of tuberculosis through granulomas-tracking. Furthermore, the loaded rifampicin was released through the dissociation of disulfide bond by the localized GSH in granulomas, realizing the targeted tuberculosis therapy and providing an especially accurate treatment mapping for tuberculosis. Thus, this targeted theranostic strategy for tuberculosis exhibits the potential to realize both granulomas-tracking and anti-infection of tuberculosis.

摘要

结核病(TB)是一种具有高传染性和高致死率的恶性传染病,会给全球带来负担,尤其是潜伏感染构成的无法抑制的威胁。构建有效的结核病防控策略具有重要意义。幸运的是,我们发现肉芽肿具有较高的还原水平,这可能是由内部炎症和相对封闭的微环境所致。因此,我们开发了首个用于结核病的靶向谷胱甘肽(GSH)响应型诊疗系统(RIF@Cy5.5-HA-NG),其负载利福平(RIF)的近红外发射载体通过光点击反应驱动的疏水-疏水相互作用构建而成,能够通过追踪肉芽肿实现结核病的早期诊断。此外,负载的利福平通过肉芽肿中局部存在的谷胱甘肽使二硫键解离而释放,实现了结核病的靶向治疗,并为结核病提供了特别精确的治疗图谱。因此,这种针对结核病的靶向诊疗策略具有实现追踪肉芽肿和抗结核感染的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c2/8883117/3568b855b383/fmolb-09-845179-g005.jpg

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