Visible Tracking of Small Molecules of Gases with Fluorescent Donors

Abstract

Biological gasotransmitters (small molecules of gases) play important roles in signal transduction mechanisms and disease treatments. Although a large number of small-molecule donors have been developed, visualizing the release of small molecules remains challenging. Owing to their unique optical properties, fluorophores have been widely applied in cellular imaging and tracking. Researchers have used various fluorophores to develop small-molecule donors with fluorescent activity for visualizing the release of small molecules and their related therapies. These include fluorophores and their derivatives such as boron-dipyrromethene (BODIPY), coumarin, 1,8-naphthalimide, hemicyanine, porphyrin, rhodamine, and fluorescein. In this review, we summarize the design concepts of functional fluorescent small-molecule donors in terms of different types of fluorophores. Then, we discuss how these donors release small molecules, and the imaging modalities and biomedical applications facilitated by their fluorescent properties. With the systematic discussion of these publications, we hope to provide useful references for the development of more practical, advanced fluorescent small-molecule donors in the future.

Figure 1

(I) (A,B) The structure characteristics of BIBCl-PAE NPs, the mechanism underlying the release of ¹O₂, and the resulting fluorescence alterations. (C) The generation of ¹O₂ by BIBCl-PAE NPs in HepG2 cells was assessed using DCFH-DA and SOSG. (D) Fluorescence imaging was performed in vivo on BALB/c mice bearing HepG2 tumors after intravenous administration of BIBCl-PAE NPs. Reproduced from ref (23). Copyright 2020 Royal Society of Chemistry. (II) (E) Upon aggregation, the fluorophore undergoes a transition to a PSs (ISC on), leading to fluorescence quenching and the generation of reactive ROS. Conversely, when the PSs are in a disaggregated state, they revert back to a fluorophore state (ISC off), resulting in fluorescence restoration without the production of ROS. (F) The structural composition of B ODIPYs derivatives. Reproduced from ref (26). Copyright 2021 Chinese Chemical Society. (III) (G) The structure characteristics of DBs and TB, the mechanism underlying the release of O₂^–•. (H) The pathway of light-induced generation of O₂^–• by α,β-linked BODIPYs. Reproduced from ref (27). Copyright 2019 Wiley-VCH GmbH.

Figure 2

(I) (A) The structure characteristics of NOD545a–g, the mechanism underlying the release of NO, and the resulting fluorescence alterations. (B–C) Cell confocal imaging and NO quantification. Reproduced from ref (38). Copyright 2016 American Chemical Society. (II) (D–E) The structure characteristics of NAB, the mechanism underlying the release of NO, and the resulting fluorescence alterations. Reproduced from ref (42). Copyright 2019 Royal Society of Chemistry. (III) (F) Schematic representation of PEG-NORM nanoparticles self-assembly. (G) The structure characteristics of PEG-NORM, the mechanism underlying the release of NO, and the resulting fluorescence alterations. (H) Effect of PEG-NORM on longevity of C. elegans. Reproduced from ref (45). Copyright 2020 Royal Society of Chemistry. (IV) (I) The structure characteristics of HSD560, the mechanism underlying the release of H₂S, and the resulting fluorescence alterations. (G) The time-dependency of Cys-triggered HSD560. (K) Fluorescence imaging of H₂S release in vivo by HSD560. Reproduced from ref (46). Copyright 2021 Royal Society of Chemistry.

Figure 3

(I) (A–B) The structure characteristics of CouN(NO)-R, the mechanism underlying the release of NO, and the resulting fluorescence alterations. Reproduced from ref (58). Copyright 2021 Wiley-VCH GmbH. (II) (C–D) The structure characteristics of SUT-1 and SUT-2, the mechanism underlying the release of H₂S, and the resulting fluorescence alterations. Reproduced from ref (62). Copyright 2020 Royal Society of Chemistry. (III) (E) The structure characteristics of BDP-NAC, the mechanism underlying the release of RSSH. (F) The structure characteristics of BDP-fluor, the mechanism underlying the release of RSSR, and the resulting fluorescence alterations. (IV) (G) The structure characteristics of CNNO, the mechanism underlying the release of NO, and the resulting fluorescence alterations. (H) Light-triggered CNNO induces vasodilation in mice by releasing NO. Reproduced from ref (69). Copyright 2017 Royal Society of Chemistry.

Figure 4

(I) (A) The structure characteristics of PEO-b-PFNM, the mechanism underlying the release of CO, and the resulting fluorescence alterations. (B) CO released by PEO-b-PFNM under light irradiation can promote wound healing in a full-thickness mouse skin wound model. Reproduced from ref (79). Copyright 2020 Royal Society of Chemistry. (II) (C) The structure characteristics of PTT-HF, the mechanism underlying the release of CO, and the resulting fluorescence alterations. (D) PTT-HF for the treatment of skin wounds. Reproduced from ref (80). Copyright 2021 Wiley-VCH GmbH. (III) (E) The structure characteristics of FB, the mechanism underlying the release of CO, and the resulting fluorescence alterations. (F) Fluorescence imaging of NO release in zebrafish by FB and its induction of vasodilation. Reproduced from ref (83). Copyright 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (IV) (G) The structure characteristics of PCNO, the mechanism underlying the release of CO, and the resulting fluorescence alterations. (H) Schematic illustration of visible light-mediated corelease of NO and CO from PCNO micelles. (I) Evaluation of therapeutic efficacy of PCNO against MRSA infection in mice. Reproduced from ref (84). Copyright 2021 Wiley-VCH GmbH.

Figure 5

(I) (A) The structure characteristics of Cyl-DNBS, the mechanism underlying the release of SO₂ and ¹O₂, and the resulting fluorescence alterations. (B) Schematic diagram of a mouse model for in vivo cancer therapy using Cyl-DNBS. Reproduced from ref (96). Copyright 2021 Wiley-VCH GmbH. (II) (C–D) The structure characteristics of NIR-HMPC, the mechanism underlying the release of CO₂, and the resulting fluorescence alterations. Reproduced from ref (97). Copyright 2020 American Chemical Society. (III) (E) The structure characteristics of APN-Cyl, the mechanism underlying the release of ¹O₂, and the resulting fluorescence alterations (F) Fluorescence imaging of tumors in Balb/c mice using APN-Cyl was conducted to monitor endogenous APN levels over a 150 min. Reproduced from ref (98). Copyright 2020 Elsevier Ltd.