Research progress of near-infrared fluorescence probes based on indole heptamethine cyanine dyes in vivo and in vitro

Abstract

Near-infrared (NIR) fluorescence imaging is a noninvasive technique that provides numerous advantages for the real-time in vivo monitoring of biological information in living subjects without the use of ionizing radiation. Near-infrared fluorescent (NIRF) dyes are widely used as fluorescent imaging probes. These fluorescent dyes remarkably decrease the interference caused by the self-absorption of substances and autofluorescence, increase detection selectivity and sensitivity, and reduce damage to the human body. Thus, they are beneficial for bioassays. Indole heptamethine cyanine dyes are widely investigated in the field of near-infrared fluorescence imaging. They are mainly composed of indole heterocyclics, heptamethine chains, and N-substituent side chains. With indole heptamethine cyanine dyes as the parent, introducing reactive groups to the parent compounds or changing their structures can make fluorescent probes have different functions like labeling protein and tumor, detecting intracellular metal cations, which has become the hotspot in the field of fluorescence imaging of biological research. Therefore, this study reviewed the applications of indole heptamethine cyanine fluorescent probes to metal cation detection, pH, molecules, tumor imaging, and protein in vivo. The distribution, imaging results, and metabolism of the probes in vivo and in vitro were described. The biological application trends and existing problems of fluorescent probes were discussed.

Keywords: Biological application; Indole heptamethine cyanine dyes; Near-infrared fluorescence probes; Research progress.

Fig. 1

Structures of indole heptamethine cyanine dyes

Fig. 2

Structure of probe 1

Fig. 3

Structure of probe 2

Fig. 4

Structure of probe 3

Fig. 5

Structure of probe 4

Fig. 6

Structures of probes 5 and 6

Fig. 7

Structures of probes 7, 8, and 9

Fig. 8

Structures of probes 10 and 11

Fig. 9

Structures of probes 12, 13, and 14

Fig. 10

Structures of probes 15–18

Fig. 11

Structure of probe 19

Fig. 12

Structure of probe 20

Fig. 13

Structures of probes 21 and 22

Fig. 14

Probes 23–25 with pH-sensitive activities

Fig. 15

Probes 26–28 with pH-sensitive activities

Fig. 16

Structure of probe 29

Fig. 17

Structure of probes 30–32

Fig. 18

Structure of probe 33

Fig. 19

Molecular structure and the proposed mechanism for O₂^·− and Hg²⁺ associated detection

Fig. 20

Structure of probe 35

Fig. 21

Structures of probes 36 and 37

Fig. 22

Possible sensing mechanism of 38 CyBS with Hg²⁺

Fig. 23

Structures of probes 39, 40, and 41

Fig. 24

Structures of probes 42, 43 and 44

Fig. 25

Structure of probe 45

Fig. 26

Structures of probes 46 and 47

Fig. 27

Structure of probe 48

Fig. 28

Structure of probe 49

Fig. 29

Structures of probes 50 and Cy-4

Fig. 30

Structures of probes 51, HCy-Mito, and Hcy-Biot

Fig. 31

Structures of probes 52 and 53

Fig. 32

Structure of probe 54

Fig. 33

Structures of probes 55, 56, 57, and 58

Fig. 34

Structures of probes 59 and 60

Fig. 35

Structure of probe 61

Fig. 36

Structure and photochemical mechanism of NO fluorescent probe

Fig. 37

Structures of probes Cy-Dise and 54

Fig. 38

Structure of probe 65

Fig. 39

Structure of probe 66

Fig. 40

Structure of probe 67

Fig. 41

Structure of probe HMC

Fig. 42

Structure of probe 68

Fig. 43

Structure of probe 69

Fig. 44

Structure of probe 70

Fig. 45

Structure of probe 71

Fig. 46

Structure of probe 72

Fig. 47

Structures of probes 73 and 74

Fig. 48

Structures of probes 75, 76 and IRDye800CW-SAHA

Fig. 49

Structures of probes 77 and 78

Fig. 50

Structure of probe 79

Fig. 51

Structure of probe 80

Fig. 52

Structures of probes IR-783, CyI, and ND-PG-Cy7

Fig. 53

Structures of probes 81–84

Fig. 54

Structure of probe 85

Fig. 55

Structure of probe NIR820-Tf

Fig. 56

Structures of probes MitoCy-NH₂ and MitoHCy-NH₂