F枚rster Resonance Energy Transfer Switchable Self-Assembled Micellar Nanoprobe: Ratiometric Fluorescent Trapping of Endogenous H2S Generation via Fluvastatin-Stimulated Upregulation

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• 作者：Chunchang Zhao ; Xiuli Zhang ; Kaibin Li ; Shaojia Zhu ; Zhiqian Guo ; Lili Zhang ; Feiyi Wang ; Qiang Fei ; Sihang Luo ; Ping Shi ; He Tian ; Wei-Hong Zhu
• 刊名：Journal of the American Chemical Society
• 出版年：2015
• 出版时间：July 8, 2015
• 年：2015
• 卷：137
• 期：26
• 页码：8490-8498
• 全文大小：563K
• ISSN：1520-5126

文摘

H₂S produced in small amounts by mammalian cells has been identified in mediating biological signaling functions. However, the in situ trapping of endogenous H₂S generation is still handicapped by a lack of straightforward methods with high selectivity and fast response. Here, we encapsulate a semi-cyanine-BODIPY hybrid dye (BODInD-Cl) and its complementary energy donor (BODIPY1) into the hydrophobic interior of an amphiphilic copolymer (mPEG-DSPE), especially for building up a ratiometric fluorescent H₂S nanoprobe with extraordinarily fast response. A remarkable red-shift in the absorption band with a gap of 200 nm in the H₂S response can efficiently switch off the F枚rster resonance energy transfer (FRET) from BODIPY1 to BODInD-Cl, subsequently recovering the donor fluorescence. Impressively, both the interior hydrophobicity of supramolecular micelles and electron-withdrawing nature of indolium unit in BODInD-Cl can sharply increase aromatic nucleophilic substitution with H₂S. The ratiometric strategy based on the unique self-assembled micellar aggregate NanoBODIPY achieves an extremely fast response, enabling in situ imaging of endogenous H₂S production and mapping its physiological and pathological consequences. Moreover, the amphiphilic copolymer renders the micellar assembly biocompatible and soluble in aqueous solution. The established FRET-switchable macromolecular envelope around BODInD-Cl and BODIPY1 enables cellular uptake, and makes a breakthrough in the trapping of endogenous H₂S generation within raw264.7 macrophages upon stimulation with fluvastatin. This study manifests that cystathione 纬-lyase (CSE) upregulation contributes to endogenous H₂S generation in fluvastatin-stimulated macrophages, along with a correlation between CSE/H₂S and activating Akt signaling pathway.