This book chapter will comment on fluorescent reporter proteins and nanocrystals’ applicability as fluorescent markers. Fluorescent reporter proteins in the Drosophila model system offer a degree of specificity that allows monitoring cellular and biochemical phenomena in vivo, such as autophagy, mitophagy, and changes in the redox state of cells. Titanium dioxide (TiO2) nanocrystals (NCs) have several biological applications and emit in the ultraviolet, with doping of europium ions can be visualized in the red luminescence. Therefore, it is possible to monitor nanocrystals in biological systems using different emission channels. CdSe/CdS magic-sized quantum dots (MSQDs) show high luminescence stability in biological systems and can be bioconjugated with biological molecules. Therefore, this chapter will show exciting results of the group using fluorescent proteins and nanocrystals in biological systems.
- fluorescent proteins
- fluorescent markers
- magic-sized quantum dots
- titanium dioxide
Several types of tools have been developed in order to monitor biological processes through fluorescence images. Some of these tools are the use of fluorescent proteins and nanomaterials. This book chapter will comment in particular on green fluorescent protein and luminescent nanocrystals.
The green fluorescent protein (GFP) of Jellyfish
One of the best and most used
The development of different nanoscale materials has increased for different applications. Titanium dioxide (TiO2) nanocrystals (NCs) have been used in several types of cosmetics, food, and the textile industry [9, 10]. This is because this NC has a wide variety of properties that improve materials, such as its bioluminescence and chemical stability . Bioluminescent techniques are widely used in biomedicine for studies of drug screening, molecular markers, and monitoring of molecular reactions, among other applications . Bioluminescent NCs, such as TiO2, present an excellent opportunity to obtain ultra-sensitive and enhanced analyzes and images, in addition to allowing the study of bioluminescence [13, 14, 15]. The use of bioluminescent imaging in vivo allows the visualization of biological processes in intact living organisms, providing abundant quantitative space–time information beyond the reach of conventional in vitro tests and fixed material .
Doping is a technique that allows the incorporation of substitutional ions into the crystalline structure of materials, generating exciting properties . TiO2 nanocrystals (NCs) with europium ions incorporated in their structure can be visualized in red fluorescence . This acquired property makes it possible to track luminescence, thus being able to be coupled to biomolecules and drugs for studies of effects and tracking them, for example, which can assist in the studies of quantitative monitoring of molecular reactions and cellular behaviors, allowing a better understanding of the functions dynamic and complicated biological phenomena [18, 19].
Quantum dots (QDs) of cadmium chalcogenides (CdSe, CdS, and CdTe) absorb and emit in the visible electromagnetic spectrum, and for this reason, they are used in several applications of biological and biomedical marking, such as fluorescent probes, biosensors, and others. In the area of biological labeling, the great applicability of QDs occurs because they present several advantages over traditional organic fluorophores, such as a long fluorescence life span, ~ 100 times greater, which allows to distinguish it from the background b signal, seen that autofluorescence has a much shorter fluorescence life; absorption and emission spectra tunable; high photo resistance and chemo-degradation; and high fluorescence intensity [20, 21, 22]. However, this comparison of the fluorescence intensity of the QDs was performed in non-aqueous solvents, with unconjugated QDs, and in non-biological media, since the fluorescence intensity may be lower when the QDs are conjugated and used in biological labeling experiments .
Ultra-small PQs (USPQs) are nanocrystals with extremely small sizes, presenting strong quantum confinement effects, in which most of their atoms are located on the surface . A large number of atoms on the surface and the presence of several pendant bonds lead to changes in the properties of nanocrystals, which can be observed in the fluorescence spectra .
The quantum dots of magic-sized (MSQDs) are nanocrystals with extremely small sizes (<2 nm) and that present physical property utterly different from traditional QDs . Although MSQDs have similar properties to USQDs, including composition and size, some fundamental properties place these QDs in different classes. The characteristic properties of MSQDs are thermodynamically stable structures, wide luminescence range, high size stability over time, relatively narrow absorption spectra and/or heterogeneous (discontinuous) growth [27, 28, 29, 30, 31]. The structures are thermodynamically stable; they are formed from the arrangement of a certain number of atoms, which gives it high stability. Nguyen et al. made theoretical predictions of different types of CdSe MSQDs structures aligned with the literature’s experimental results . The term magic size is related to a (magic) number of atoms in the structure that makes QDs extremely stable . The broad luminescence spectrum occurs due to MSQDs having internal atomic defects (absence or extra presence of atoms) [27, 29, 32].
The development of new alternatives for the study of biomolecules in organic systems has grown considerably. The high specificity and sensitivity of scientific methodologies based on fluorescence clarify biological events . Fluorescent probes based on organic dyes have been shown to identify biomolecules [34, 35]. Silva et al. demonstrated that the biocompatibility of CdSe/CdS MSQRd could be tuned in the synthesis,  present high luminescence stability in biological systems , can be bioconjugated with several biomolecules aiming at the most diverse luminescent probes [38, 39, 40, 41, 42] and in biosensors [43, 44].
This chapter shows recent results that the group has been working with fluorescent reporter proteins and the applicability of nanocrystals as fluorescent markers. Nanocrystals of pure and europium doped TiO2 and CdSe/CdS (MSQDs) will be some of the exciting tools for marking in biological systems.
2. Fluorescent proteins and nanocrystals
This section will show the group results using GFP tagged proteins and nanocrystals’ applicability as fluorescent markers.
2.1 Drosophila lines expressing fluorescent proteins
In 2011, Albrecht et al. established a monitoring system that allows assessing the status of chemically defined redox species (the redox pair GSH/GSSH and H2O2) in subcellular compartments cytosol and mitochondria
Figure 2 shows three different transgenic lines of
2.2 Nanocrystals as luminescent markers (nanomarkers)
Figure 3 shows exciting results on pure and europium (Eu) doped TiO2 NCs. TiO2 NCs absorb and emit in the ultraviolet, but when incorporating the europium ions in its crystalline structure, by replacing some titanium ions, it shows luminescence in red. The colors emitted by the pure and Eu doped TiO2 NCs (Figure 3a), and the crystalline structure in the anatase phase (Figure 3b) are illustrated. Also, in Figure 3c, the emission spectra of these nanocrystals are observed.
In order to investigate whether TiO2 and TiO2:Eu nanocrystals could be tracked on adult
In order to distinguish between intrinsic fluorescence from fat body and TiO2 fluorescence, the pixel intensity was measured and compared among all fat body spheres of control images and TiO2 treated samples. As we can observe in the graphic in Figure 5a there was a drastic increase in fluorescence due to the presence of TiO2. The fat body spheres of the control animals (Figure 4E and G) also showed intrinsic fluorescence when excited with red light; however, when the animals have exposed to TiO2:Eu the intensity of fluorescence was higher (Figure 4F and H). The pixel intensity analysis showed that the presence of TiO2:Eu caused a significant increase in fluorescence (Figure 5b). The observation that the NCs of TiO2 and TiO2:Eu could be detected in the fat body of newly emerged adult animals indicates that the bioaccumulation of nanocrystals during larval development persisted until the beginning of the adult stage. Surprisingly, we observed that animals dissected on the second day of its emergence no longer had fat bodies fluorescent spheres containing nanocrystals. This may indicate that one day following the emergence, the animals were able to excrete the NC. The disappearance of nanocrystals may also be related to the rapid absorption of the fat body during the first days of life. Similar results were described by Jovanovic et al. 2016, which observed that animals that received TiO2 during the larval stage did not have TiO2 as adults .
The optical properties and illustration of CdSe/CdS are shown in Figure 6. The aqueous solution and the illustration of the core/shell structure of CdSe/CdS MSQDs with a surfactant are exemplified to facilitate understanding (Figure 6
Bioimaging assays are biological applications QDs since they can be bioconjugated with proteins, antibodies, and DNA [39, 48, 49]. In general, these tests depend on the biocompatibility of QDs, which is obtained by functionalizing the surface of these nanoparticles [39, 50, 51, 52]. The bioconjugation allows the study and tracking of biomolecules in biological systems such as cell cultures and laboratory animals [53, 54]. The versatility of QDs associated with maltose-binding protein for intracellular delivery of the drug beta-cyclodextrin . Other studies have used the quantum dots for
The tracking and study of biomolecules labeled with QDs in vitro and in vivo is a reality in several areas, allowing us to analyze the location and distribution of bioconjugate in biological systems. Silva et al. demonstrated that the CdSe/CdS MSQDs could be bioconjugated with several biomolecules aiming at the most diverse luminescent probes [38, 39, 40, 41, 42] in biosensors [43, 44]. Dias et al. labeled a phospholipase A2 isolated from
In this chapter, we have shown that fluorescent reporter proteins in the
This work was supported by grants of CNPq, CAPES, FAPEAL, and FAPEMIG.
Conflict of interest
The authors declare no conflict of interest.
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