We hope that the herein-discussed reports will inspire the researchers working in the field of fluorescence sensing compounds and drug delivery to develop new chemosensing materials with improved practical biomedical applications. Theranostic agents are macromolecular conjugates including a covalently bonded antitumor drug, imaging marker, and targeting component. As targeting agents use high-affinity molecules, such as antibodies, peptides or peptide fragments, aptamers, etc., their role is to target theranostics to specific molecular targets present in cancer cells. The imaging agents are needed to identify and locate the tumor before treatment, provide imaging information about the delivery and distribution of the theranostic platform in the tumor, and obtain feedback on the therapeutic effect after treatment 157.
After 3 h of incubation (lower panel), green emissions of A375 enhanced prominently while blue emissions quenched significantly. Green emissions indicate the endogenous catalysis of probe 14. Jang et al. proposed the phototheranostic small molecule 68 (meso-carboxylate-BODIPY—chlorambucil), which is chemically stable under assay conditions 174. Upon light activation of the conjugate in water, both the drug molecule and the dye are released, which leads to an increase in luminescence by about 1250 times; no toxic nitroso photoproducts products are formed in this process (Figure 64).
Fluorescent Probes Based on Photoinduced Electron Transfer (PET)
AND logic gate 50 with two inputs (H+ and Na+) and singlet oxygen as output 152. Chemical structure of 37 and schematic illustration of its ratiometric Zn2+ sensing mechanism 119. Fluorescence images of organs and tumors of tumor-bearing mice after tail vein administration of 17 (100 µM). Fluorescence image of the AD model mice (left panel) and in vitro fluorescence staining of 15 on age-matched Tg mouse (right panel)—APP/PS1 transgenic, male.
As a result, the changes in neural signals were visualized in real time. Fluorophores are very useful and sensitive labels for biomolecules, and fluorescent labels are by far the most common labels used for synthetic oligonucleotides. Many different fluorophores can be readily attached to oligonucleotides to create fluorescent probes, which form the basis of the detection systems used in DNA sequencing, forensic science and genetic analysis. In drug-delivery systems, the drug is bound to a fluorescent molecule by means of a non-degradable linkage in a drug-fluorescent dye conjugate (non-cleavable conjugates) or with a biodegradable linker to form cleavable conjugates (Figure 52).
Figure 42.
Here, we have briefly discussed recent developments of fluorophore–drug conjugates for use in cancer therapy. Fluorescent imaging in theranostics gives new insights into cancer therapy at cellular and molecular levels because it illuminates pathways of drug transport, distribution, and accumulation. Structure and the single crystal structure of probe 42. The ratiometric images of the lysosomal pH distribution of HeLa cells without stimulants (left image) and stimulated with 10 mM acetic acid incubated for 8 min at 37 °C (right image). Confocal images of 35 responding to HOCl in HepG2 cells. HepG2 cells were incubated with 35 (10.0 μM) for 15 min prior to incubating with HOCl (20 equiv.) for 15 min.
Figure 4.
The anticancer hydrophobic drug doxorubicin (DOX), is covalently attached to the side chain of the water-soluble polymer poly(fluorene-co-ethynylene) (PFE) via the acid-sensitive acylhydrazone bond in conjugate 67. The fluorescence of the conjugated PEE is effectively quenched by the energy/electron transfer (ET) between DOX and the polymer. Worldtradex scam In addition, the amphiphilic polymer skeleton as the drug delivery vehicle contributes to the uptake of the hydrophobic drug by cancer cells. The acidic microenvironment of cancer cells ensures the effective drug release induced by the breakage of the acylhydrazone bond, which results in the fluorescence recovery of the conjugated polymer, contributing to the monitoring of the drug release process.
Molecular wire PET 31 depends upon the voltage-sensitive electron transfer from an electron-rich donor (orange) through a membrane-spanning molecular wire (black) to a fluorescent reporter (green). At hyperpolarizing potentials, the electric field is aligned antiparallel to the direction of electron transfer, resulting in efficient PET and quenched fluorescence (left). Depolarization aligns the electric field in the direction of PET, decreasing the rate of electron transfer, and increasing fluorescence (right). Tyrosinase is a polyphenolic oxidase enzyme with clinical importance due to its association with the https://worldtradex.biz/ progress of some diseases such as Parkinson, dopamine neurotoxicity, schizophrenia, and melanoma cancer 73,74,75.
- Intracellular viscosity is an index affecting physiological processes that affect the transport, diffusion, and interactions between biomolecules.
- This conjugation with an appropriate modification of one side chain of the heptamethine carbocyanine dye did not change the electronic properties of the aromatic backbones in order to maintain the fluorescence and tumor-specific targeting properties.
- As we mentioned above, the FRET process is strongly distance dependable.
Therefore, reaction-based probes are indeed unsuitable for dynamic imaging during a long-term process. It should be pointed out that most fluorescent probes are essentially monochromatic, and such probes are susceptible to interference from external factors. The single-parameter input model of traditional imaging cannot accurately reflect the interactions between multianalyte changes in physiological and pathological-state complicacy and dynamic variation in living organisms. Synchronous imaging for multiple analytes during a certain pathophysiological process can provide cross information on the pathology that is highly desirable. Therefore, the rational design of probes for the synchronous imaging of multiple analytes can be achieved.
This makes the synthesized probes a potential tool for the early diagnosis of mitochondrial-related diseases. This focused attention of Zhang et al. to prepare mitochondria-accessing ratiometric fluorescent probe 12 capable of detecting selectively superoxide anions 71. As a receptor fragment in probe 12, a triphenylphosphonium unit was introduced in which the diphenylphosphinate part trigged selective oxidation in the presence of superoxide anions.
Figure 14.
Thanks to their extremely small size, molecular logic devices can penetrate and work in living organisms without endangering their lives. This makes them an integral part of biomechatronics, as they can provide real-time communication between a living object and a machine or device. Molecular logic devices have potential for real-world applications such as object coding, image reproduction, intelligent materials for medical diagnostics, and drug release and activation 151. Molecular computation is particularly useful for real-time rapid diagnostics in biology and medicine. Such molecular devices can save time for doctors and can ensure safe conditions in epidemics due to analyses performed by the molecular device itself. The AIE probes are widely used for the effective visualization of lipid droplets 138,139,140.
Figure 59.
As can be seen in Figure 18, isolated, and incubated in 20 μM of the probe, solutions of sample heart, liver, spleen, lung, kidney, and tumor are presented, where the tumor shows significantly higher fluorescence over the organs. Together with these results, probe 17 showed low toxicity and good biocompatibility, which makes it an excellent tool for tumor visualization. The ICT donor–acceptor–donor mode is an interesting approach for the design of an NIR probe for bioimaging.
Based on the observed changes, a ratiometric analysis was obtained and implemented for pH measurements in living cells. However, due to the different acidity of both receptors, the 5 and 6 were suitable for pH determination at different pH windows. Compound 5 showed a pKa value of 6.73 and fluorescence response from pH 7.5 to pH 6.0, while the pKa of probe 6 was calculated to be 4.98, which makes it useful for pH measurements ranging between 5.5 and 4.6. Due to the higher acidity, 6 was applied for the detection of pHs in lysosomes, which are known as acid organelles.
Fluorescent Probes Based on Fluorescent Resonance Energy Transfer (FRET)
- As a ROS agent connected to different diseases, peroxynitrite (ONOO−) also is an object of intracellular PET fluorescent imaging and observation.
- Depolarization aligns the electric field in the direction of PET, decreasing the rate of electron transfer, and increasing fluorescence (right).
- The disulfide was used as a selective cleavage reactive recognition unit for glutathione.
- Molecule 66, encapsulated into liposomes with particle sizes in the range of 60 ≈ 100 nm, ensures permeability and a retention effect.
- In presence of Hg2+, the fluorescence of 1 was blue-shifted to 663 nm due to the lowered ICT efficiency as a result of the Hg2+ chelating process in which the lone electron pair on the nitrogen participated.
- In diagnostic studies, the analyte-related output signals, dependent on the optical properties of the probes, are vital for the diagnosis of diseases.
This tutorial review introduces some important concepts related to fluorescent probe development. It is hoped that it will facilitate further expansion of the field by demystifying it. The free probe 35 displayed a strong broad fluorescence at 515 nm and a large Stokes shift of 155 nm, which was assigned to the ESIPT process.
