Real-time Near-infrared Fluorescent Reporting the Azoreductase-triggered Drug Release
Real-time Near-infrared Fluorescent Reporting the Azoreductase-triggered Drug Release
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实时近红外荧光报告偶氮还原酶触发的药物释放
DOI：
10.1039/c9py01365b
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Xiulin Zhu
中科院分区：
文献类型：
--
作者：
Yuqing Wang;Jiawei Yu;Zhe Wang;Shahid Iqbal;Wei Zhang;Zhengbiao Zhang;Nianchen Zhou;Xiulin Zhu
近红外荧光探针由于其高效、灵敏、可忽略体内背景干扰等优点，在生物传感和生物成像中发挥着重要作用。偶氮苯衍生物表现出众所周知的光敏感性，并且是药物递送和生物检测中独特的酶响应候选物，因为偶氮双键可以被偶氮还原酶裂解。本文合成了一种新型的具有生物相容性的两亲性嵌段共聚物近红外探针。偶氮苯基团与近红外荧光基团AzaBODIPY（硼-二吡咯亚甲基）连接亲水性（PEG）和疏水性（PLA）片段，形成两亲性嵌段共聚物PEG-AzaBODIPY-AZO-PLA。PEG 398-AzaBODIPY-AZO-PLA 144自组装成载药球形胶束。由于聚集诱导猝灭（ACQ）效应，自组装体是无荧光的。在偶氮还原酶的作用下，PEG和PLA链段由于偶氮键的断裂而断开。这导致胶束的分解和随后的胶囊化药物的释放。在拆卸时，通过消除ACQ效应激活近红外荧光的发射。溶液中自组装体的荧光强度随着药物释放而不断增强。荧光报告药物释放显示了在生物传感和人体结肠药物控制释放方面的潜在应用。
A near-infrared fluorescent probe plays an important role in biosensing and bioimaging because of its high efficiency, sensitivity and negligible background interference in vivo. Azobenzene derivatives demonstrate well-known sensitivity to light and are unique enzyme-responsive candidates in drug delivery and biological detection because the azo double bond can be cleaved by azoreductase. Herein, a novel near-infrared probe of an amphiphilic block copolymer with biological compatibility was synthesized. The azobenzene group attached with the near-infrared fluorescent group AzaBODIPY (boron-dipyrromethenes) linked the hydrophilic (PEG) and hydrophobic (PLA) segments to form the amphiphilic block copolymer PEG-AzaBODIPY-AZO-PLA. PEG398-AzaBODIPY-AZO-PLA144 self-assembled into drug-loaded spherical micelles. The self-assemblies were non-fluorescent owing to the aggregation-induced quenching (ACQ) effect. Triggered by azoreductase, the PEG and PLA segments were disconnected due to the cleavage of the azo bond. This caused the disassembly of the micelles and the subsequent release of the encapsulated drug. Upon disassembly, the emission of the near-infrared fluorescence was activated by the elimination of the ACQ effect. Furthermore, the fluorescence intensity of the self-assemblies in solution increased continuously with drug release. The fluorescence reporting drug release demonstrates the potential applications in biosensing and controlled drug release in the colon of the human intestine.