UV Light as an Efficient Tool for Reducing Surface Defects of ZnSe-MSA Quantum Dots.

Defects in ZnSe quantum dots are responsible for increasing the trap states, which can lead to the drastic reduction of their fluorescence output, being one of the major drawbacks of these materials. As surface atoms become more relevant in these nanoscale structures, energy traps due to surface vacancies, play a very definite role in the final emission quantum yield. In the present study, we report the use of photoactivation procedures to decrease surface defects of ZnSe QDs stabilized with mercaptosuccinic acid (MSA), in order to improve the radiative pathways. We applied the colloidal precipitation procedure in a hydrophilic medium and evaluated the role of Zn/Se molar ratios as well as the Zn2+ precursors (nitrate and chloride salts) on their optical properties. Best results (i.e. increment of 400% of the final fluorescence intensity) were obtained for nitrate precursor and a Zn/Se = 1.2 ratio. Thus, we suggest that the chloride ions may compete more efficiently than nitrate ions with MSA molecules decreasing the passivation capability of this molecule. The improvement in ZnSe QDs fluorescence can potentialize their use for biomedical applications.

CdTe quantum dots as fluorescent probes to study transferrin receptors in glioblastoma cells.

BACKGROUND: Overexpression of transferrin receptors (TfRs), which are responsible for the intracellular uptake of ferric transferrin (Tf), has been described in various cancers. Although molecular biology methods allow the identification of different types of receptors in cancer cells, they do not provide features about TfRs internalization, quantification and distribution on cell surface. This information can, however, be accessed by fluorescence techniques. In this work, the quantum dots (QDs)' unique properties were explored to strengthen our understanding of TfRs in cancer cells. METHODS: QDs were conjugated to Tf by covalent coupling and QDs-(Tf) bioconjugates were applied to quantify and evaluate the distribution of TfRs in two human glioblastoma cells lines, U87 and DBTRG-05MG, and also in HeLa cells by using flow cytometry and confocal microscopy. RESULTS: HeLa and DBTRG-05MG cells showed practically the same TfR labeling profile by QDs-(Tf), while U87 cells were less labeled by bioconjugates. Furthermore, inhibition studies demonstrated that QDs-(Tf) were able to label cells with high specificity. CONCLUSIONS: HeLa and DBTRG-05MG cells presented a similar and a higher amount of TfR than U87 cells. Moreover, DBTRG-05MG cells are more efficient in recycling the TfR than the other two cells types. GENERAL SIGNIFICANCE: This is the first study about TfRs in human glioblastoma cells using QDs. This new fluorescent tool can contribute to our understanding of the cancer cell biology and can help in the development of new therapies targeting these receptors.

Highly fluorescent and superparamagnetic nanosystem for biomedical applications.

This work reports on highly fluorescent and superparamagnetic bimodal nanoparticles (BNPs) obtained by a simple and efficient method as probes for fluorescence analysis and/or contrast agents for MRI. These promising BNPs with small dimensions (ca. 17 nm) consist of superparamagnetic iron oxide nanoparticles (SPIONs) covalently bound with CdTe quantum dots (ca. 3 nm). The chemical structure of the magnetic part of BNPs is predominantly magnetite, with minor goethite and maghemite contributions, as shown by Mössbauer spectroscopy, which is compatible with the x-ray diffraction data. Their size evaluation by different techniques showed that the SPION derivatization process, in order to produce the BNPs, does not lead to a large size increase. The BNPs saturation magnetization, when corrected for the organic content of the sample, is ca. 68 emu g-1, which is only slightly reduced relative to the bare nanoparticles. This indicates that the SPION surface functionalization does not change considerably the magnetic properties. The BNP aqueous suspensions presented stability, high fluorescence, high relaxivity ratio (r 2/r 1 equal to 25) and labeled efficiently HeLa cells as can be seen by fluorescence analysis. These BNP properties point to their applications as fluorescent probes as well as negative T 2-weighted MRI contrast agents. Moreover, their potential magnetic response could also be used for fast bioseparation applications.

Development of Fluorescent Sensors for Biorelevant Anions in Aqueous Media Using Positively Charged Quantum Dots.

Quantum dots (QDs) have captured the attention of the scientific community due to their unique optical and electronic properties, leading to extensive research for different applications. They have also been employed as sensors for ionic species owing to their sensing properties. Detecting anionic species in an aqueous medium is a challenge because the polar nature of water weakens the interactions between sensors and ions. The anions bicarbonate (HCO3-), carbonate (CO32-), sulfate (SO42-), and bisulfate (HSO4-) play a crucial role in various physiological, environmental, and industrial processes, influencing the regulation of biological fluids, ocean acidification, and corrosion processes. Therefore, it is necessary to develop approaches capable of detecting these anions with high sensitivity. This study utilized CdTe QDs stabilized with cysteamine (CdTe-CYA) as a fluorescent sensor for these anions. The QDs exhibited favorable optical properties and high photostability. The results revealed a gradual increase in the QDs' emission intensity with successive anion additions, indicating the sensitivity of CdTe-CYA to the anions. The sensor also exhibited selectivity toward the target ions, with good limits of detection (LODs) and quantification (LOQs). Thus, CdTe-CYA QDs show potential as fluorescent sensors for monitoring the target anions in water sources.

A surface-enhanced infrared absorption spectroscopy (SEIRA) multivariate approach for atrazine detection.

A green, fast and effective multivariate method for the determination of atrazine (ATZ) was developed using conventional infrared equipment furnished with an attenuated total reflectance module (ATR-IR), providing limit of detection (LOD) and limit of quantification (LOQ) in the ranges from 1.9 to 4.6 µg/mL and from 5.6 to 14 µg/mL, respectively. Furthermore, the surface-enhanced infrared absorption (SEIRA) approach was investigated to improve the sensitivity of the measurements and detect ATZ at low concentrations, addressing the compatibility with reference methods. To this end, a substrate formed by silver selenide quantum dots stabilized with mercaptopropionic acid (Ag2Se/MPA), synthesized in aqueous medium by an one-pot synthesis, was used. The spectral data were investigated by univariate and multivariate calibrations, allowing to calculate the enhancement factor (EF) and the multivariate enhancement factor (MEF), respectively. The SEIRA strategy proved to be able to enhance the atrazine signal up to 86-fold, allowing the detection of ATZ at concentrations as low as 0.001 µg/mL.

Advances on chalcogenide quantum dots-based sensors for environmental pollutants monitoring.

Water contamination represents a significant ecological impact with global consequences, contributing to water scarcity worldwide. The presence of several pollutants, including heavy metals, pharmaceuticals, pesticides, and pathogens, in water resources underscores a pressing global concern, prompting the European Union (EU) to establish a Water Watch List to monitor the level of these substances. Nowadays, the standard methods used to detect and quantify these contaminants are mainly liquid or gas chromatography coupled with mass spectrometry (LC/GC-MS). While these methodologies offer precision and accuracy, they require expensive equipment and experienced technicians, and cannot be used on the field. In this context, chalcogenide quantum dots (QDs)-based sensors have emerged as promising, user-friendly, practical, and portable tools for environmental monitoring. QDs are semiconductor nanocrystals that possess excellent properties, and have demonstrated versatility across various sensor types, such as fluorescent, electrochemical, plasmonic, and colorimetric ones. This review summarizes recent advances (2019-2023) in the use of chalcogenide QDs for environmental sensing, highlighting the development of sensors capable of detect efficiently heavy metals, anions, pharmaceuticals, pesticides, endocrine disrupting compounds, organic dyes, toxic gases, nitroaromatics, and pathogens.

Sensitive Zika biomarker detection assisted by quantum dot-modified electrochemical immunosensing platform.

We report the development of a new nanostructured electrochemical immunosensing platform for the detection of the Zika virus envelope protein (EP-ZIKV). For this, quantum dots (QDs) were explored in combination with screen-printed carbon electrodes (SPCEs) functionalized with a conductor polymeric film, formed from 2-(1H-pyrrol-1-yl)ethanamine (Pyam), and anti-EP DIII ZIKV antibodies. Carboxylated CdTe QDs were synthesized, characterized by optical and structural techniques, and covalently immobilized onto the SPCE/PPyam surface. Then, anti-EP ZIKV antibodies were also covalently conjugated to QDs. All stages of platform assembly were evaluated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The detection of EP-ZIKV was performed by differential pulse voltammetry (DPV). Results indicated that QDs were efficiently immobilized, and did not show oxidation, under the conditions evaluated, for at least 7 months. Anti-EP ZIKV antibodies were effectively immobilized on the PPyam/QDs surface, even after 2 months of electrode storage. The platform enabled the detection of EP-ZIKV with high sensitivity using minimal sample volumes (LOD = 0.1 ng mL-1 and LOQ = 0.4 ng mL-1). The platform was also able to detect EP-ZIKV in spiked serum samples. Moreover, the platform showed specificity, not detecting the EP-DENV 3 nor a mixture of four DENV serotypes antigens. Thus, the proposed combination favored the development of a sensitive immunosensing platform, promising for the detection of Zika in the viremic phase, which also holds potential for transposition to other arboviruses.

Quantum Dots and Gd3+ Chelates: Advances and Challenges Towards Bimodal Nanoprobes for Magnetic Resonance and Optical Imaging.

The development of multimodal nanoprobes has been growing in recent years. Among these novel nanostructures are bimodal systems based on quantum dots (QDs) and low molecular weight Gd3+ chelates, prepared for magnetic resonance imaging (MRI) and optical analyses. MRI is a technique used worldwide that provides anatomic resolution and allows distinguishing of physiological differences at tissue and organ level. On the other hand, optical techniques are very sensitive and allow events to be followed at the cellular or molecular level. Thus, the association of these two techniques has the potential to achieve a more complete comprehension of biological processes. In this review, we present state-of-the-art research concerning the development of potential multimodal optical/paramagnetic nanoprobes based on Gd3+ chelates and QDs, highlighting their preparation strategies and overall properties.

Lanthanide(III) complexes of 4,10-bis(phosphonomethyl)-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (trans-H6do2a2p) in solution and in the solid state: structural studies along the series.

Complexes of 4,10-bis(phosphonomethyl)-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (trans-H(6)do2a2p, H(6)L) with transition metal and lanthanide(III) ions were investigated. The stability constant values of the divalent and trivalent metal-ion complexes are between the corresponding values of H(4)dota and H(8)dotp complexes, as a consequence of the ligand basicity. The solid-state structures of the ligand and of nine lanthanide(III) complexes were determined by X-ray diffraction. All the complexes are present as twisted-square-antiprismatic isomers and their structures can be divided into two series. The first one involves nona-coordinated complexes of the large lanthanide(III) ions (Ce, Nd, Sm) with a coordinated water molecule. In the series of Sm, Eu, Tb, Dy, Er, Yb, the complexes are octa-coordinated only by the ligand donor atoms and their coordination cages are more irregular. The formation kinetics and the acid-assisted dissociation of several Ln(III)-H(6)L complexes were investigated at different temperatures and compared with analogous data for complexes of other dota-like ligands. The [Ce(L)(H(2)O)](3-) complex is the most kinetically inert among complexes of the investigated lanthanide(III) ions (Ce, Eu, Gd, Yb). Among mixed phosphonate-acetate dota analogues, kinetic inertness of the cerium(III) complexes is increased with a higher number of phosphonate arms in the ligand, whereas the opposite is true for europium(III) complexes. According to the (1)H NMR spectroscopic pseudo-contact shifts for the Ce-Eu and Tb-Yb series, the solution structures of the complexes reflect the structures of the [Ce(HL)(H(2)O)](2-) and [Yb(HL)](2-) anions, respectively, found in the solid state. However, these solution NMR spectroscopic studies showed that there is no unambiguous relation between (31)P/(1)H lanthanide-induced shift (LIS) values and coordination of water in the complexes; the values rather express a relative position of the central ions between the N(4) and O(4) planes.

Evaluation of [Ln(H2cmp)(H2O)] metal organic framework materials for potential application as magnetic resonance imaging contrast agents.

Aqueous suspensions of metal organic frameworks (MOF) containing different Ln(3+) ions, consisting of a series of layered Ln(3+) networks formulated as [Ln(H(2)cmp)(H(2)O)] (where H(5)cmp is (carboxymethyl)iminodi(methylphosphonic acid), with a relatively wide size distribution (400 nm to 1 microm) were studied by relaxometry. The water (1)H longitudinal (r(1)) and transverse (r(2)) relaxivities were obtained for aqueous suspensions of these materials with different lanthanide ions. The values of r(1) are very small and varied only slightly with the effective magnetic moment (mu(eff)) of the lanthanide ions, while r(2) values are larger and proportional to the value of mu(eff)(2). The dependence of R(2) on tau(CP) (the time interval between two consecutive refocusing pulses in the train of 180 degrees pulses applied in a CPMG pulse sequence) was evaluated. The value of R(2) initially increases with tau(CP) and then saturates at higher tau(CP) at a value that is about 3 to 5 times lower than R(2p)*. This can be explained by the static dephasing regime (SDR) theory, in which the diffusion effect is taken into account and where the condition tau(D) > Delta omega(r(p))(-1) holds (tau(D) = r(p)(2)/D, where D is the diffusion coefficient, r(p) is the radius of the particle, and Delta omega(r(p)) is the Larmor frequency shift at the particle's surface). Separation of the particles into two fractions with different particle sizes led to a significant enhancement of the r(2) relaxivity of the smaller particles with a narrow size distribution. Magnetometric measurements performed with the particles containing Dy(III), Ho(III), and Gd(III) showed a typical paramagnetic behavior from 4 to 100 K, used to determine the Curie constants.

Quantum dots functionalized with 3-mercaptophenylboronic acids as novel nanoplatforms to evaluate sialic acid content on cell membranes.

Sialic acids (SAs) modulate essential physiological and pathological conditions, including cell-cell communication, immune response, neurological disorders, and cancer. Besides, SAs confer negative charges to cell membranes, also contributing to hemorheology. Phenylboronic acids, called as mimetic lectins, have been highlighted to study SA profiles. The association of these interesting molecules with the optical properties of quantum dots (QDs) can provide a deeper/complementary understanding of mechanisms involving SAs. Herein, we explored the thiol affinity to the QD surface to develop a simple, fast and direct attachment procedure to functionalize these nanocrystals with 3-mercaptophenylboronic acids (MPBAs). The functionalization was confirmed by fluorescence correlation spectroscopy and inductively coupled plasma spectrometry. The conjugate specificity/efficiency was proved in experiments using red blood cells (RBCs). A labeling >90% was found for RBCs incubated with conjugates, which reduced to 17% after neuraminidase pretreatment. Moreover, QDs-MPBA conjugates were applied in a comparative study using acute (KG-1) and chronic (K562) myelogenous leukemia cell lines. Results indicated that KG-1 membranes have a greater level of SA, with 100% of cells labeled and a median of fluorescence intensity of ca. 2.5-fold higher when compared to K562 (94%). Therefore, this novel QDs-MPBA conjugate can be considered a promising nanoplatform to evaluate SA contents in a variety of biological systems.

Hydrophilic Quantum Dots Functionalized with Gd(III)-DO3A Monoamide Chelates as Bright and Effective T1-weighted Bimodal Nanoprobes.

Magnetic resonance imaging (MRI) is a powerful non-invasive diagnostic tool that enables distinguishing healthy from pathological tissues, with high anatomical detail. Nevertheless, MRI is quite limited in the investigation of molecular/cellular biochemical events, which can be reached by fluorescence-based techniques. Thus, we developed bimodal nanosystems consisting in hydrophilic quantum dots (QDs) directly conjugated to Gd(III)-DO3A monoamide chelates, a Gd(III)-DOTA derivative, allowing for the combination of the advantages of both MRI and fluorescence-based tools. These nanoparticulate systems can also improve MRI contrast, by increasing the local concentration of paramagnetic chelates. Transmetallation assays, optical characterization, and relaxometric analyses, showed that the developed bimodal nanoprobes have great chemical stability, bright fluorescence, and high relaxivities. Moreover, fluorescence correlation spectroscopy (FCS) analysis allowed us to distinguish nanosystems containing different amounts of chelates/QD. Also, inductively coupled plasma optical emission spectrometry (ICP - OES) indicated a conjugation yield higher than 75%. Our nanosystems showed effective longitudinal relaxivities per QD and per paramagnetic ion, at least 5 times [per Gd(III)] and 100 times (per QD) higher than the r1 for Gd(III)-DOTA chelates, suitable for T1-weighted imaging. Additionally, the bimodal nanoparticles presented negligible cytotoxicity, and efficiently labeled HeLa cells as shown by fluorescence. Thus, the developed nanosystems show potential as strategic probes for fluorescence analyses and MRI, being useful for investigating a variety of biological processes.

Quantum dots-based fluoroimmunoassay for anti-Zika virus IgG antibodies detection.

Zika virus (ZIKV) has been declared a public health emergency of international concern. ZIKV has been associated with some neurological disorders, and their long-term effects are not completely understood. The majority of the methods for ZIKV diagnosis are based on the detection of IgM antibodies, which are the first signs of immunological response. However, the detection of IgG antibodies can be an important approach for ZIKV past infection diagnosis, especially for pregnant women, helping the comprehension/treatment of this disease. There has been a growing interest in applying nanoparticles for efficient ZIKV or antibodies detection. Quantum dots (QD) are unique fluorescent semiconductor nanoparticles, highly versatile for biological applications. In the present study, we explored the special QD optical properties to develop an immunofluorescence assay for anti-ZIKV IgG antibodies detection. Anti-IgG antibodies were successfully conjugated with QDs and applied in a fluorescence sensing nanoplatform. After optimization using IgG antibodies, the conjugates were employed to detect anti-ZIKV IgG antibodies in polystyrene microplates sensitized with ZIKV envelope E protein. The nanoplatform was able to detect anti-ZIKV IgG antibodies in a concentration at least 100-fold lower than the amount expected for protein E immune response. Moreover, conjugates were able to detect the antibodies for at least 4 months. Thus, our results showed that this QDs-based fluoroimmunoplatform can be considered practical, simple and promising to detect Zika past infections and/or monitoring immune response in vaccine trials.

Multimodal highly fluorescent-magnetic nanoplatform to target transferrin receptors in cancer cells.

BACKGROUND: Site-specific multimodal nanoplatforms with fluorescent-magnetic properties have great potential for biological sciences. For this reason, we developed a multimodal nanoprobe (BNPs-Tf), by covalently conjugating an optical-magnetically active bimodal nanosystem, based on quantum dots and iron oxide nanoparticles, with the human holo-transferrin (Tf). METHODS: The Tf bioconjugation efficiency was evaluated by the fluorescence microplate assay (FMA) and the amount of Tf immobilized on BNPs was quantified by fluorescence spectroscopy. Moreover, relaxometric and fluorescent properties of the BNPs-Tf were evaluated, as well as its ability to label specifically HeLa cells. Cytotoxicity was also performed by Alamar Blue assay. RESULTS: The FMA confirmed an efficient bioconjugation and the fluorescence spectroscopy analysis indicated that 98% of Tf was immobilized on BNPs. BNPs-Tf also presented a bright fluorescence and a transversal/longitudinal relaxivities ratio (r2/r1) of 65. Importantly, the developed BNPs-Tf were able to label, efficiently and specifically, the Tf receptors in HeLa cells, as shown by fluorescence and magnetic resonance imaging assays. Moreover, this multimodal system did not cause noteworthy cytotoxicity. CONCLUSIONS: The prepared BNPs-Tf hold great promise as an effective and specific multimodal, highly fluorescent-magnetic, nanoplatform for fluorescence analyses and T2-weighted images. GENERAL SIGNIFICANCE: This study developed an attractive and versatile multimodal nanoplatform that has potential to be applied in a variety of in vitro and in vivo studies, addressing biological processes, diagnostic, and therapeutics. Moreover, this work opens new possibilities for designing other efficient multimodal nanosystems, considering other biomolecules in their composition able to provide them important functional properties.

Fine tuning of the relaxometry of γ-Fe2O3@SiO2 nanoparticles by tweaking the silica coating thickness.

We report the fine-tuning of the relaxometry of gamma-Fe2O3@SiO2 core-shell nanoparticles by adjusting the thickness of the coated silica layer. It is clear that the coating thickness of Fe2O3@SiO2 nanoparticles has a significant impact on the r(1) (at low B0 fields), r(2), and r(2)* relaxivities of their aqueous suspensions. These studies clearly indicate that the silica layer is heterogeneous and has regions that are porous to water and others-that are not. It is also shown, that the viability and the mitochondrial dehydrogenase expression of the microglial cells do not appear to be sensitive to the vesicular load with these core-shell nanoparticles. The adequate silica-shell thickness can therefore be tuned to allow for both a sufficiently high response as contrast agent, and-adequate grafting of targeted biomolecules.

NMR transversal relaxivity of aqueous suspensions of particles of Ln(3+)-based zeolite type materials.

A series of zeolite-type silicates containing stoichiometric amounts of Ln(3+) ions in the framework (Ln-AV-9 materials), with composition (Na(4)K(2))(Ln(2)Si(16)O(38)).10H(2)O (Ln = Nd, Sm, Eu, Tb, Gd, Dy) has recently been synthesized and characterized. They form paramagnetic microparticles, which as aqueous suspensions have negligible water (1)H longitudinal relaxivities (r(1)) for all Ln(3+) ions studied and quite large transverse relaxivities (r(2)). In this work we further analysed the size distribution of the Ln-AV-9 particles and their r(2)* and r(2) relaxivities. The r(2)* relaxivity effects are explained by the static dephasing regime (SDR) theory. The r(2) relaxivities appear to be strongly dependent on the interval between two consecutive refocusing pulses (tau(CP)) in the train of 180 degrees pulses applied. For long tau(CP) values, the r(2) of the systems saturates at a value, which is always an order of magnitude smaller than r(2)*. These features are explained by a crude model, which takes into account the residual diffusion effect in the static dephasing regime. The large microparticles, although not efficient in T(1) relaxation, are quite effective in enhancing T(2) relaxation, particularly at high magnetic fields. The r(2)* values and the saturation values for r(2) were found to increase linearly with B(0) and mu(0)(2). The largest transversal relaxation rate enhancements were observed for Dy-AV-9 with a saturation value of r(2) of 60 s(-1) mM(-1) and a r(2)* value of 566 s(-1) mM(-1) at 9.4 T and 298 K.