title: Förster Resonance Energy Transfer Switchable Self-Assembled Micellar Nanoprobe: Ratiometric Fluorescent Trapping of Endogenous H2S Generation via Fluvastatin-Stimulated Upregulation.
abstract: 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 Förster 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 γ-lyase (CSE) upregulation contributes to endogenous H2S generation in fluvastatin-stimulated macrophages, along with a correlation between CSE/H2S and activating Akt signaling pathway.
authors.affiliation: †Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, Collaborative Innovation Center for Coal Based Energy (i-CCE), East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Chunchang
authors.initials: C
authors.lastname: Zhao
authors.affiliation: †Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, Collaborative Innovation Center for Coal Based Energy (i-CCE), East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: †Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, Collaborative Innovation Center for Coal Based Energy (i-CCE), East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Kaibin
authors.initials: K
authors.lastname: Li
authors.affiliation: ‡State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Shaojia
authors.initials: S
authors.lastname: Zhu
authors.affiliation: †Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, Collaborative Innovation Center for Coal Based Energy (i-CCE), East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Guo
authors.affiliation: †Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, Collaborative Innovation Center for Coal Based Energy (i-CCE), East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.affiliation: †Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, Collaborative Innovation Center for Coal Based Energy (i-CCE), East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Feiyi
authors.initials: F
authors.lastname: Wang
authors.affiliation: †Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, Collaborative Innovation Center for Coal Based Energy (i-CCE), East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fei
authors.affiliation: †Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, Collaborative Innovation Center for Coal Based Energy (i-CCE), East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Sihang
authors.initials: S
authors.lastname: Luo
authors.affiliation: ‡State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Shi
authors.affiliation: †Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, Collaborative Innovation Center for Coal Based Energy (i-CCE), East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: He
authors.initials: H
authors.lastname: Tian
authors.affiliation: †Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, Collaborative Innovation Center for Coal Based Energy (i-CCE), East China University of Science and Technology, Shanghai 200237, P. R. China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000737:chemistry; D003542:Cystathionine gamma-Lyase / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D005456:Fluorescent Dyes / Q000737:chemistry; D000077340:Fluvastatin; D006862:Hydrogen Sulfide / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008823:Micelles; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D000067996:RAW 264.7 Cells; D015854:Up-Regulation
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D007211:Indoles; D008823:Micelles; D011108:Polymers; D000077340:Fluvastatin; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide