That is why the intracellular imaging of these ions could Worldtradex company reviews be an excellent diagnostic tool. Thus, the chemosensing properties of probe 33 were tested after the incubation of MDA-MB cells with 20 μM of the probe. It was found that 33 showed excellent intracellular response toward the cations Zn2+ and Mg2+. In addition, the MTT assay indicated very low cytotoxicity. Recently, Mahapatra et al. obtained compound 34, which was designed as a ratiometric fluorescent probe for the determination of F− anions 109. It is well known that a higher concentration of fluoride induces apoptosis, causes fluorosis, and leads to nephrotoxic changes and urolithiasis in humans 110,111,112.
The meso-Cl conjugate 60 (Figure 56) showed 100-fold enhanced cytotoxicity over the parent anaplastic lymphoma kinase inhibitor 164. This improvement is even more pronounced (492-fold) when the above conjugate is combined with temozolomide—a standard drug for the treatment of glioblastoma. Self-assembly of probe 20 with Rhodamine 110 into amphiphilic polymer PS-PEG to form nanoparticles 20RF NPs and illustration of intracellular temperature sensing. Proposed mechanism in CPT activation and fluorescent variation of the prodrug 64 by the treatment of GSH 168. Compound 51 induces apoptosis and then switches to diagnostic mode and fluorescently tags apoptotic cells.
- This reactive recognition mechanism was confirmed using mass spectroscopic analysis (Figure 35).
- Chemical system 49 performs AND logic operation under the action of two chemical inputs (H+ and Na+) and the corresponding truth table 150.
- Furthermore, 9 showed good biocompatibility and low toxicity.
Figure 14.
This encouraged Huang et al. to synthesize probe 4, which was able to coordinate Cu2+ and Hg2+ 47. Probe 4 was designed as an ICT-based NIR fluorescence ratiometric probe, which makes it a promising candidate for real-time imaging in living organisms (Figure 5). This probe has a bright emission at 730 nm and contains an electron-donating amino group as a metal recognition unit that takes place in a strong ICT process during excitation. In the presence of Hg2+, the probe fluorescence was blue-shifted to 673 nm due to the binding of Hg2+ with electron-donating amines that reduced the ICT efficiency. Based on the observed fluorescent changes, a ratiometric analysis was constructed, which showed a value of 5.23 in the presence of Hg2+, and 0.37 in its absence. In addition, this probe was able to coordinate Cu2+ but it was found that the observed complex was non-fluorescence.
- In acid media, the probes change their green emissions in red fluorescence due to the protonation of the electron-accepting heterocyclic nitrogen that enhanced its electron deficiency and ICT efficiency, respectively.
- Schematic illustration of the proposed activation mechanism of probe 41.
- This change was about 10 nm more than the one in 6, where the fluorescence maximum was shifted from 517 to 555 nm.
- First, FRET-based systems offer long communication wavelengths (excitation energy and observed fluorescence signal) resulting in a large pseudo-Stokes shift.
The recent advances in the design and synthesis of drug conjugates for fluorescent monitoring in drug delivery and tumor therapy are discussed in several reviews 22,23,24,157,158. The disulfide was used as a selective cleavage reactive recognition unit for glutathione. The energy-accepting BODIPY had weak fluorescence emissions and an absorption at 705 nm, which well overlapped with the highly fluorescent emissions of the energy-donating BODIPY. In the presence of glutathione, the disulfide linker was cut off and both the chromophoric units were separated. Thus, the FRET process was interrupted and the strong fluorescence of the energy-donating BODIPY at 698 nm was emitted.
Figure 6.
For example, Zhang et al. prepared probes 43 and 44 to monitor lipid droplets for the diagnosis and treatment of atherosclerotic heart diseases (Figure 44) 141. Both probes (43 and 44) were designed on the acceptor–π–donor–π–acceptor model with malononitriles as the electron-acceptor groups, thiophene fragment as a π-bridge, and triphenylamine or 4-methoxy triphenylamine as an electron-donor. Both compounds showed low fluorescence emission in solution or in the aggregated state.
PPT release mechanism of the activatable prodrug by treatment of GSH. In vivo imaging of nude mice bearing tumor after intravenous injection of (A) 63 (1 mg/kg PPT) and (B) mPEG-DSPE/63 (1 mg/kg PPT) at various time points (0.5, 1, 2, 6, and 24 h). Ex vivo fluorescence images of the different organs of mice, including kidney, lung, spleen, liver, heart, and tumor, which were sacrificed at 24 h post-injection with (C) 63 and (D) mPEG-DSPE/63. Choi and co-workers 165 synthesized a new drug–dye conjugate 61 (Figure 56), which is a combination of the poly ADP ribose polymerase (PARP) inhibitor rucaparib and heptamethine cyanine dye 60. The resulting compound demonstrated strong cytotoxic activity with nanomolar potency in three different patient-derived glioblastoma cell lines. The observed potency is at least 780-fold higher than the modified rucaparib.
Figure 17.
An interesting example of the ESIPT probe for the detection of biologically relevant cations was that prepared by Singh et al., namely, compound 33 108. Probe 33 has a very weak fluorescent emission at 450 nm that was attributed to the possible ESIPT in this molecule (Figure 33). In the presence of Zn2+ and Mg2+, due to the deprotonation of 33 in the binding process with these cations, the ESIPT was blocked and new bright fluorescent emissions were observed.
Figure 55.
During excitation, such systems undergo donor–acceptor charge transfer from the donor to acceptor that results in “charge-polarized” excited states with a positively charged electron-donor site. The subsequent change in the dipole moment leads to a Stokes shift, which is strongly microenvironmentally dependable. This makes ICT systems a very suitable platform for sensing designing, as the presence of a charged guest nearby the donor or acceptor moiety changes the ICT efficiency and, respectively, the fluorophore photophysical properties.
The reversibility is another important parameter. Usually, the microenvironments during a pathophysiological process fluctuate with time. The irreversible probe just reflects the microenvironmental changes in one direction, upregulation or downregulation, which cannot fulfill the real dynamic monitoring.
In acid media, a rhodamine spirolactam was protonated to a xanthene form that induced FRET from the 1,8-naphthalimide unit, whereby red rhodamine fluorescence appeared. As a result, the fluorescent micelles with the entrapped probe 40 demonstrated a highly pH-sensitive response in water. They are also internalized into HeLa and HEK cells and showed low cytotoxicity and good imaging properties. Moreover, in Hella cells, the fluorescence micelles possessed much better photostability in comparison to the pure organic dye label such as BODIPY. Similar to the ESIPT, the FRET signaling output has some benefits in the construction of fluorescent probes for biomedical applications. First, FRET-based systems offer long communication wavelengths (excitation energy and observed fluorescence signal) https://worldtradex.pro/ resulting in a large pseudo-Stokes shift.
In 39, a spirolactam-closed rhodamine was coupled to a yellow-green emitting 1,8-naphthalimide through a thiohydrazide recognition spacer. It should be noted that after the opening of a rhodamine spirolactam form, FRET is already transformed into TBET. In the case of FRET, a non-conjugated spacer links the donor and acceptor, while at TBET, the donor and acceptor are directly connected via an electronically conjugated bond. The obtained ratiometric signaling revealed a linear response at concentrations of 0–5 µM and a detection limit of 14.5 nM. Meanwhile, 39 was successfully applied to image intracellular HOCl and targeted lysosomes with low cytotoxicity. A typical ICT-based probe for metal cations is compound 1, which possesses a chelate unit NS2O2 for the highly sensitive and selective detection of Hg2+ ions (Figure 2).
Figure 40.
The probe was successfully applied for the imaging of cancer in mice in vivo and in different mice organs ex vivo. Moreover, the released fluorescent BODIPY was an efficient photodynamic agent with negligible dark toxicity. The revealed photodynamic antitumor performance at high glutathione concentrations made this compound an excellent photosensitizer for selective cancer treatment. In addition, an overview of recent achievements in the development of fluorescence probes as molecular logic devices with biomedical application was provided. Moreover, the implementation of the above photophysical phenomena in fluorescence–drug conjugates for theranostic and drug delivery systems is revealed.
Low cytotoxicity of the probe was confirmed using MTS assays against HeLa, 293 A, and HepG2. Zn2+ is another important metal cation whose intracellular detection could be useful for diagnostic purposes. This ion is involved in pathological processes, such as Alzheimer’s disease, epilepsy, ischemic stroke, infantile diarrhea, apoptosis, disorder of enzyme regulation, and neurotransmission. Recently, Ahmed et al. synthesized compound 3 as a useful ICT-based fluorescent probe for intracellular measurements of Zn2+ 46.
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