Nitroso-caged upconversion luminescent prodrug: Near infrared light-activatable NO nano-donor for gas therapy
Nitroso-caged upconversion luminescent prodrug: Near infrared light-activatable NO nano-donor for gas therapy
复制标题
亚硝基笼上转换发光前药：用于气体治疗的近红外光可激活 NO 纳米供体
DOI：
10.1016/j.cej.2021.132858
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发表时间：
2021-10-21
影响因子：
15.1
通讯作者：
Liu, Yi
中科院分区：
文献类型：
--
作者：
Tiemuer, Aliya;Yu, Hui;Liu, Yi
气体疗法已经成为一种有效的癌症治疗方法，具有最小的组织侵入性和很少的耐药性。特别是一氧化氮（NO）气体传递剂在高浓度下具有直接的抗癌效果，引起了广泛的关注。然而，目前的NO前药的主要缺点是NO递送到靶组织的不足和缺乏时空精确释放的能力。同时，也低估了NO前体药物实现实时深部组织药物监测可视化的高灵敏度，以可靠的递送确认。本文合成了两种近红外（NIR）光触发的NO释放供体（NRh-Bn-NO和NRh-Et-NO），用于具有极好的时空可控性的NO递送，同时通过频率上转换发光（FUCL）读出来追踪介导的药物释放。FUCL是一种独特的反斯托克斯发光成像模式，具有上级成像灵敏度和高分辨率的信噪比，在深部肿瘤成像中具有优先地位。此外，用NRh-Bn-NO构建纳米系统（PEG-Bn-NO），以保证通过直接NIR活化有效地产生NO，同时允许深度的高分辨率药物监测。静脉内给药后，PEG-Bn-NO特异性靶向肿瘤部位，并选择性控制由NIR光诱导的肿瘤生长。NO纳米前药应该是与实时药物递送监测集成的高效气体疗法的启发。
Gas therapy has emerged as an effective cancer treatment for minimal tissue invasiveness and little drug resistance. Particularly, Nitric oxide (NO) gas transmitter has drawn extensive attention for direct cancer-killing efficiency at high concentrations. However, the major drawbacks of the current NO prodrugs are insufficient NO delivery to the target tissues and lack the ability of spatiotemporal release precision. Meanwhile, it is also underestimated for NO prodrugs to achieve real-time deep-tissue drug monitoring visualization with high sensitivity for reliable delivery confirmation. Herein, two near infrared (NIR) light-triggered NO-releasing donors (NRh-Bn-NO and NRh-Et-NO) are synthesized for NO delivery with superb spatiotemporal controllability while tracing drug release mediated by frequency upconversion luminescence (FUCL) readout. FUCL is a unique antiStokes luminescence imaging modality that provides superior imaging sensitivity and increased signal-to-noise ratio for high resolution, which takes precedence in deep-seated tumor imaging. Furthermore, a nano-system (PEG-Bn-NO) is constructed with NRh-Bn-NO to guarantee efficient NO generation by direct NIR activation while allowing high-resolution drug monitoring in depth. Following intravenous administration, PEG-Bn-NO is specifically targeted to the tumor site and selectively controlled tumor growth induced by NIR light. The NO nano-prodrug should be inspirational to highly efficient gas therapy integrated with real-time drug delivery monitoring.