A rational design of a cancer-specific and lysosome-targeted fluorescence nanoprobe for glutathione imaging in living cells
A rational design of a cancer-specific and lysosome-targeted fluorescence nanoprobe for glutathione imaging in living cells
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用于活细胞谷胱甘肽成像的癌症特异性和溶酶体靶向荧光纳米探针的合理设计
DOI：
10.1039/d0ma00124d
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发表时间：
2020
影响因子：
5
通讯作者：
Jian Chen
中科院分区：
文献类型：
--
作者：
Hong Wang;Peisheng Zhang;Chonghua Zhang;Shu Chen;Rongjin Zeng;Jiaxi Cui;Jian Chen
开发一种针对特定癌细胞溶酶体的多功能探针，随后检测谷胱甘肽（GSH）水平，对于揭示谷胱甘肽在癌细胞溶酶体氧化应激中的作用至关重要。在此，我们展示了一种制备双靶向（癌细胞和溶酶体靶向）荧光纳米探针（DTFN）的有效策略，该探针能够成像特定癌细胞溶酶体中的谷胱甘肽。将叶酸（FA）修饰的光稳定聚集诱导发射点与gsh响应的二氧化锰（MnO2）纳米片通过静电相互作用结合得到纳米探针（DTFN）。DTFN具有水分散性好、光稳定性好、响应时间短（~ 5 min）、ph响应范围宽等特点。细胞内实验表明，制备的DTFN可通过FR介导的内吞作用优先内化到叶酸受体（FR）阳性的癌细胞中。随后，借助纳米探针带正电的氨基部分，DTFN可以选择性地在溶酶体中积累，成功实现fr阳性癌细胞溶酶体GSH水平的实时成像。本研究强调了一种设计多功能双靶向荧光探针的策略，用于增强癌症成像。
Developing a versatile probe for targeting the lysosomes of specific cancer cells and subsequently detecting glutathione (GSH) levels is critical in disclosing the roles of GSH in the lysosomal oxidative stress of cancer cells. Herein, we demonstrate an efficient strategy for the preparation of a dual-targeting (both cancer cell- and lysosome-targeting) fluorescence nanoprobe (DTFN) that enables the imaging of GSH in the lysosomes of specific cancer cells. The nanoprobe (DTFN) is obtained by combining folic acid (FA)-modified photostable aggregation-induced emission dots with GSH-responsive manganese dioxide (MnO2) nanosheets via electrostatic interactions. DTFN has outstanding characteristics of good water dispersity, delightful photostability, shorter responsive time (∼5 min) and wide pH-response range. Intracellular experiments showed that the as-prepared DTFN could be preferentially internalized into a folate receptor (FR)-positive cancer cells via the FR-mediated endocytosis. Subsequently, with the aid of the positively charged amino moiety of the nanoprobe, DTFN can selectively accumulate in lysosomes and successfully achieve the real-time imaging of the lysosomal GSH levels in FR-positive cancer cells. This study highlights a strategy to design a versatile dual-targeting fluorescence probe for enhanced cancer imaging.