Upconversion Fluorescent Nanoparticles Research Articles

Quantum optical immunoassay: upconversion nanoparticle-based neutralizing assay for COVID-19

In a viral pandemic, a few important tests are required for successful containment of the virus and reduction in severity of the infection. Among those tests, a test for the neutralizing ability of an antibody is crucial for assessment of population immunity gained through vaccination, and to test therapeutic value of antibodies made to counter the infections. Here, we report a sensitive technique to detect the relative neutralizing strength of various antibodies against the SARS-CoV-2 virus. We used bright, photostable, background-free, fluorescent upconversion nanoparticles conjugated with SARS-CoV-2 receptor binding domain as a phantom virion. A glass bottom plate coated with angiotensin-converting enzyme 2 (ACE-2) protein imitates the target cells. When no neutralizing IgG antibody was present in the sample, the particles would bind to the ACE-2 with high affinity. In contrast, a neutralizing antibody can prevent particle attachment to the ACE-2-coated substrate. A prototype system consisting of a custom-made confocal microscope was used to quantify particle attachment to the substrate. The sensitivity of this assay can reach 4.0 ng/ml and the dynamic range is from 1.0 ng/ml to 3.2 upmug/ml. This is to be compared to 19 ng/ml sensitivity of commercially available kits.

Quantifying contrast of latent fingerprints developed by fluorescent nanomaterials based on spectral analysis

Fluorescent nanoparticles (NPs) have been used to develop latent fingerprints with enhanced contrast. However, a method for quantifying the contrast is still lacking, making it impossible to achieve quantitative comparison in the contrast enhancement between different fingerprint developing agents. Here we proposed a new method to quantify the developed contrast using two indexes when fluorescent NPs were used to develop the latent fingerprint. One is the intensity index (I) defined as the ratio between the integrated fluorescence intensities of the signal and background in the fluorescence spectra of the developed fingerprint. Another is the chroma index (C) determined from the color difference between developed fingerprints and their substrates in the chromaticity graph. We defined the developed contrast as the product of the chroma index and the common logarithm of the intensity index (C·lg I), and validated this method using both down- and up-conversion fluorescent NPs and on a variety of different substrates (glass, marble, red paper and money). We showed that the developed contrast quantified by our method effectively reflected the true contrast but the intensity or chroma index alone was not always effective. This work opens up a new avenue to quantifying and enhancing the developed contrast.

Remotely Ameliorating Blood Glucose Levels in Type 2 Diabetes Via a Near‐Infrared Laser

AbstractType 2 diabetes, lowly responsive to insulin injection, is a difficult chronic disease which requires therapeutic breakthroughs. Herein, a new concept is proposed to remotely control the glucose metabolism by a near‐infrared (NIR) laser for the treatment of type 2 diabetes for the first time. This method integrates fluorescent upconversion nanoparticles with the optogenetic technique to selectively activate the phosphoinositide 3‐kinase/AKT signaling pathways, in an insulin‐independent manner for type 2 diabetic treatments. It features fast responsiveness (in seconds) to NIR, deep tissue penetration (up to centimeters), and tunable dosage by adjusting laser irradiation. Successful glucose metabolic regulation has been demonstrated both in vitro and in vivo, thus offering the possibility of developing new alternative strategies to meet the clinical challenges in the treatment of type 2 diabetes.

Semiquantitative immunochromatographic colorimetric biosensor for the detection of dexamethasone based on up-conversion fluorescent nanoparticles.

A low-cost bifunctional immunochromatographic colorimetric biosensor was developed that can be read visually or by using an optical density scanner. Five test lines (T lines) coated with different antigens were set on a nitrocellulose (NC) membrane to indicate the concentration of analyte. This method was applied for the detection of dexamethasone. The corresponding detection range was 0.1-9ngmL-1, and the detection limit for dexamethasone in food supplements and cosmetic samples was 2.0μgkg-1. For visual inspection of the colour the quantitative relative error range between the proposed method and liquid chromatography was -62 to -25%, with a detection time of only 10min. More accurate assay results were obtained by using an optical density scanner with the relative error range of -31 to 20%. The results indicated that the proposed method has the potential of applicationfor rapid and efficient screening of dexamethasone in cosmetics and food supplements. Graphical abstract.

Ultra-sensitive detection of malathion residues using FRET-based upconversion fluorescence sensor in food.

Malathion is an organophosphorus pesticide which could remain in agricultural products and exert irreversible harmful effects on human health. Hence, strict monitoring of malathion contents is very significant. Here, a highly sensitive fluorescent aptasensor was developed for the determination of malathion, the system was based on a cationic polymer-mediated fluorescence 'turn-off'. In this system, malathion-specific aptamers were bound to cationic polymer through electrostatic interactions. To produce fluorescence resonance energy transfer (FRET), negatively charged upconversion fluorescent nanoparticles (UCNPs) and cationic-polymer encapsulated gold nanoparticles (GNPs) were combined. This combination resulted in fluorescence quenching, and the degree of quenching was correlated with the concentration of malathion. Under optimum conditions, the fluorescence intensities were observed to decrease linearly with the rising concentration of the malathion from 0.01 to 1μM with a detection limit of 1.42nM. Furthermore, the developed sensor possessed good selective recognition ability for malathion and was successfully used to detect malathion in adulterated tap water and matcha samples with high accuracy.

Colloidal clusters of icosahedrons and face-centred cubes

Synthetically colloidal clusters with new functions and well-controlled size distribution can in principle be constructed using colloidal particles. The building units could be integrated into dense-packed and desired structured with novel functions by means of an efficient strategy or binding patterns. Here we synthesized colloidal clusters of icosahedrons and long-range ordered face-centered cubes (FCCs) via emulsion self-assembly using fluorescence upconversion nanoparticles NaGdF4: Yb3+, Er3+ as building blocks. The icosahedrons and FCCs structure may generate spontaneously due to an entropy-driven process. The morphology and structure of colloidal clusters have noticeable transformation from icosahedron-like symmetry to FCC symmetry with the increasing size of clusters. Furthermore, the colloidal clusters could be decorated with cationic polyethyleneimine (PEI) via electrostatic interaction. When copper ions are added, the amino groups of PEI could coordinate with Cu2+ forming low toxic PEI-Cu2+ layers, which can further serve as energy receptors to quench upconversion fluorescence with 980 nm laser excitation. Our results reflect that the colloidal clusters not only can serve as a fluorescence platform of detection and analysis but also may represent advancement in the field of colloidal and interface sciences.

Synthesis of highly fluorescent RhDCP as an ideal inner filter effect pair for the NaYF4:Yb,Er upconversion fluorescent nanoparticles to detect trace amount of Hg(II) in water and food samples

In the present work, a new approach is established for the selective and sensitive detection of trace amount of Hg(II) using spirolactam appended rhodamine-B based organic complex-RhDCP and upconversion-luminescent nanoparticles mixed system. Highly stable and water dispersable upconversion-luminescent nanoparticles and organic complex RhDCP was synthesized, characterized and confirmed. The developed RhDCP- upconversion-luminescent nanoparticles (NaYF4: Yb, Er) sensing probe exhibited pronounced selective enhancement in the absorption intensity and fluorescence quenching in the presence of Hg(II) ions. Based on the quantitative reaction between the (RhDCP and Hg(II)), a significant spectral overlap between the emission and absorption bands of upconversion-luminescent nanoparticles and RhDCP- Hg(II) occurred thereby resulting in inner filter effect induced emission quenching. At different optimal conditions, the RhDCP-upconversion fluorescence quenching efficiency was proportional to the concentration of Hg(II) owing to the inner filter effect. The proposed sensing strategy could sensitively detect Hg(II) as low as 13.5 nM. The practical applicability of the developed sensing method is established by carrying out sensing experiments in real sample analysis.

Synthesis of OA-NaYF4:Yb,Er and Its Cytotoxicity

Upconversion fluorescent nanoparticles have attracted a lot of attention from scientists with a series of excellent fluorescence properties and have become a research hotspot in the field of bioimaging. In this article, upconversion fluorescent nanoparticles were successfully prepared and their biological toxicity was studied.

Simultaneous Sensing of Seven Pathogenic Bacteria by Guanidine-Functionalized Upconversion Fluorescent Nanoparticles.

The method capable of simultaneously detecting multiple target bacterial pathogens is necessary and of great interest. In this research, we demonstrated our initial effort to simultaneously detect seven common foodborne bacteria by developing a straightforward upconversion fluorescence sensing approach. The fluorescent nanosensor was constructed from a designed guanidine-functionalized upconversion fluorescent nanoparticles (UCNPs@GDN), tannic acid, and hydrogen peroxide (HP) and could quantify pathogenic bacteria in a nonspecific manner because the luminescence of the upconversion fluorescent nanoparticle was effectively strengthened in the presence of bacteria. When the developed nanosensor was applied to quantify multiple bacteria including Escherichia coli, Salmonella, Cronobacter sakazakii, Shigella flexneri, Vibrio parahaemolyticus, Staphylococcus aureus, and Listeria monocytogenes, a linear range of 103 to 108 cfu mL–1 and a detection limit of 1.30 × 102 cfu mL–1 have been obtained for the seven model mixture bacteria. In addition, the similar linear range and detection limit were also obtained for the detection of single bacteria. The present approach also exhibited acceptable recovery values ranging from 70.0 to 118.2% for bacteria in real samples (water, milk, and beef). All these results suggested that the guanidine-functionalized upconversion fluorescent nanosensor could be considered as a promising candidate for the rapid detection and surveillance of microbial pollutants in food and water.

Investigation of rare earth upconversion fluorescent nanoparticles in biomedical field

Abstract Rare earth upconversion nanoparticles (UCNPs) with the superior performance in the biomedical field have attracted great attention. Due to the good light stability, low toxicity, deep tissue penetration and excellent bio-compatibility, UCNPs display great potential for development in the biomedical field. Excellent related reports are increasing year by year, like molecular sensing, bioimaging and therapeutics. In this paper, the preparation, modification, application of upconversion fluorescent nanoparticles and the latest research results in the field of biomedical materials have been reported in detail. Graphical abstract: In this paper, we systematically summarize and describe the preparation, modification, application and latest discovery in biomedical field of rare earth upconversion nanoparticles (UCNP). Due to the good light stability, low toxicity, deep tissue penetration and excellent biocompatibility, UCNPs display superior performance for the development of biomedical field in cancer therapy. Our work will certainly inspire researchers in related fields to create more meaningful upconversion nanomaterials and do more contributions to human cancer treatment research.

An aptamer based aggregation assay for the neonicotinoid insecticide acetamiprid using fluorescent upconversion nanoparticles and DNA functionalized gold nanoparticles.

An acetamiprid-binding aptamer (ABA), gold nanoparticles (AuNPs) and upconversion nanoparticles (UCNPs) are used in a colorimetric and fluorometric method for the ultrasensitive and selective detection of the pesticide acetamiprid. The ABA is first configured into a duplex with a complementary DNA covalently attached to AuNPs. The resulting dsDNA-functionalized AuNP probe is not stable in 0.15M NaCl solution and aggregates. This causing the color to change from red to purple. In the presence of acetamiprid, the ABA undergoes a structural switch from a DNA duplex to an aptamer-acetamiprid complex and consequently dissociates from the AuNPs. The partially unhybridized AuNPs are stable against salt-induced aggregation and show red color. The ratio of absorbances at 524nm (red) and 650nm (purple blue) varies with the concentration of acetamiprid in the 0.025-10μM concentration range. The colorimetric signal can be further amplified by introducing DNA-modified carboxylated UCNPs (silica-coated NaYF4:Yb,Er) which display red and green fluorescence under 980nm excitation. An inner filter effect occurs between DNA-modified UCNPs and dsDNA-modified AuNPs. The fluorometric assay is based on the measurement of the ratio of red (654nm) and green (540nm) fluorescence and works in the 0.025 to 1μM acetamiprid concentration range and has a 0.36nM detection limit (at a signal-to-noise ratio of 3). Because of the specificity of the aptamer, the assay is high selective. It was successfully used to quantify acetamiprid in contaminated real samples. Graphical abstract Schematic presentation of an upconversion fluorescent assay for acetamiprid. It involves the principle of analyte-triggered structural switch of aptamers, salt-induced AuNP aggregation, and signal amplification from UCNP.

Upconversion fluorescent nanoparticles based-sensor array for discrimination of the same variety red grape wines.

In this research, a novel fluorescent sensor array based on upconversion nanomaterials (UCNPs) for the discrimination of the same variety red grape wines from different manufacturers was developed. The sensor array was composed of six elements: one positively charged UCNPs modified with guanidine groups (UCNPs@GDN), two negatively charged UCNPs modified with sulfonic acid groups (UCNPs@SO3H) and phosphonic acid groups (UCNPs@PO(OH)2), respectively, and their mixture 1 (UCNPs@GDN + UCNPs@SO3H), mixture 2 (UCNPs@GDN + UCNPs@PO(OH)2) and mixture 3 {UCNPs@GDN + UCNPs@SO3H + UCNPs@PO(OH)2}. The discrimination mechanism is mainly attributed to the emission of those upconversion fluorescent nanoparticles being quenched by organic ingredients that usually exist in red grape wines. The discrimination of red grape wines was carried out by employing UCNPs@GDN, UCNPs@SO3H and UCNPs@PO(OH)2 in pH = 7.0 HEPES buffer, the mixture 1 and mixture 2 in pH = 9.0 PBS buffer, and mixture 3 in pH = 6.0 Tris–HCl buffer. Principal component analysis (PCA) of the data obtained from our established array showed obvious distinction among the nine red grape wines from different manufacturers. The present work is expected to inspire more marvellous research in the fields of UCNPs and red grape wines identification.

White up-conversion efficiency of Yb3+/Er3+/Tm3+ co-doped β-NaYF4 nano-crystals

In this paper, Yb3+/Er3+, Yb3+/Tm3+ and Yb3+/Er3+/Tm3+ co-doped β-NaYF4 up-conversion fluorescent nanoparticles (UCNPs) with an average diameter of 50 nm were successfully synthesized through a thermal decomposition method. The Yb3+/Er3+ co-doped UCNPs possess bright and tunable luminescence varying from green to red as the ratio of Yb3+ and Er3+ doping increases. Remarkably, white up-conversion luminescence can be successfully achieved through the incorporation of Tm3+. The white light up-conversion efficiency of Yb3+/Er3+/Tm3+ co-doped UCNPs dispersed in the solvent have been calculated, suggesting the potentials of the efficient white up-conversion emissions for the multispectral imaging and potential bio-applications.

Heterostructures of MOFs and Nanorods for Multimodal Imaging

AbstractMultifunctional heterostructures fabricated by assembling individual components are identified as a potential theranostic tool in biological fields, representing a strategy of great significance. Herein, heterodimers of the zeolitic imidazolate framework (ZIF)‐8 and gold nanorods (Au NRs) are designed and synthesized for collaborative photothermal treatment and chemotherapy triggered by near‐infrared (NIR) light. Furthermore, Ag2S, Ag2Se, upconversion fluorescent nanoparticles, and doxorubicin hydrochloride loaded into the ZIF‐8 are released after intravenous injection. This release is attributed to the pH‐responsive system, which simultaneously enabled computed tomography, photoacoustic, and NIR fluorescence imaging for tumors. Under NIR irradiation using an 808 nm laser, the tumor can be completely eliminated in vivo through multimodal imaging‐guided chemophotothermal treatment. Overall, the present study makes several noteworthy contributions to the efficient diagnosis and treatment of cancer using the metal‐organic framework‐assisted heterodimer as a versatile nanoplatform.

Lanthanide ions doped in vanadium oxide for sensitive optical glucose detection

Blood glucose monitoring is essential to avoid the unwanted consequences of glucose level fluctuations. Optical monitors are of special interest because they can be non-invasive. Among optical glucose sensors, fluorescent upconversion nanoparticles (UCNPs) have the advantage of good photostability, low toxicity, and exceptional autofluorescence suppression. However, to sense glucose, UCNPs normally need surface functionalization, and this can be easily affected by other factors in biological systems, and may also affect their ability for real-time sensing of both increasing and decreasing glucose levels. Here, we report YVO4 : Yb3+, Er3+@Nd3+ core/shell UCNPs with Nd and Yb shell and GdVO4 : Yb3+, Er3+@Nd3+ core/shell UCNPs with Nd and Yb shell that show sensitive, reversible, and selective optical glucose detection without the need for any surface functionalization or modifications.

A test strip for ochratoxin A based on the use of aptamer-modified fluorescence upconversion nanoparticles.

An aptamer-based test strip is described for visual and instrumental determination of the mycotoxin ochratoxin A (OTA). It is based on the use of NaYF4:Yb,Er upconversion nanoparticles (UCNPs) as a label for the aptamer and on the competition between OTA and its complementary sequence for an OTA-specific aptamer. To improve the analytical performance, the optical properties of the UCNPs, the fluidity of the UCNP-aptamer conjugate, and the migration rate on the nitrocellulose membranes were investigated. Under the optimal experimental conditions and by using a 980-nm laser, the relative fluorescence intensity (test line value/control line value) is proportional to the logarithm of the OTA concentration over a range from 5 to 100ng·mL-1 (R2 = 0.9955). The limit of the detection is 1.86ng·mL-1. This aptamer based flow assay can be performed within 15min and has no serious cross-sensitivity to potentially interfering species. It was successfully applied to the determination of OTA in spiked wheat and beer samples. Graphical abstract An aptamer-based upconversion fluorescent strip based onthe use of NaYF4:Yb,Er nanoparticles was developed for sensitive detection of Ochratoxin A. The limit of the detection was determined as 1.86ng·mL-1. The assay can be performed within 15min, indicating its great potential in point-of-care testing.

Highly selective and sensitive sensing of 2,4,6-trinitrophenol in beverages based on guanidine functionalized upconversion fluorescent nanoparticles

In this study, a highly selective and sensitive fluorescent sensing method based on guanidine functionalized upconversion nanoparticles (UCNPs@GDN) for the detection of 2,4,6-trinitrophenol (TNP) has been developed. The oil-soluble UCNPs (NaYF4: Yb3+, Er3+) with the diameter of 80nm, which were synthesized by solvo-thermal method, were modified with 3-aminopropyltrimethoxysilane to obtain amine functionalized UCNPs (UCNPs@NH2). The aqueous dispersed UCNPs@GDN was obtained by changing the amine groups of UCNPs@NH2 into guanidine groups with s-ethylisothiourea hydrobromide. When excited by 980nm wavelength, UCNPs@GDN displayed three emission peaks at 365nm, 479nm and 550nm, respectively. The UCNPs@GDN exhibited strongly fluorescent quenching effect at 365nm in the presence of TNP, which can be applied to detect TNP based on fluorescence resonance energy transfer (FRET). When the concentration of TNP was in the range of 1×10−8–1×10−12M, the quenching intensity of fluorescent signal at 365nm was linear with the concentration of TNP. The detection limit of 7.78×10−13M for TNP was achieved. The present method showed high selectivity to TNP. Finally, six kinds of beverage samples containing the target were analyzed, which indicated that this method could be applied to the rapid and sensitive detection of TNP in beverages.

Upconversion nanoparticle-mediated photodynamic therapy induces autophagy and cholesterol efflux of macrophage-derived foam cells via ROS generation

Macrophage-derived foam cells are a major component of atherosclerotic plaques and have an important role in the progression of atherosclerotic plaques, thus posing a great threat to human health. Photodynamic therapy (PDT) has emerged as a therapeutic strategy for atherosclerosis. Here, we investigated the effect of PDT mediated by upconversion fluorescent nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) on the cholesterol efflux of THP-1 macrophage-derived foam cells and explored the possible mechanism of this effect. First, we found that PDT notably enhanced the cholesterol efflux and the induction of autophagy in both THP-1 and peritoneal macrophage-derived foam cells. The autophagy inhibitor 3-methyladenine and an ATG5 siRNA significantly attenuated PDT-induced autophagy, which subsequently suppressed the ABCA1-mediated cholesterol efflux. Furthermore, the reactive oxygen species (ROS) produced by PDT were responsible for the induction of autophagy, which could be blocked by the ROS inhibitor N-acetyl cysteine (NAC). NAC also reversed the PDT-induced suppression of p-mTOR and p-Akt. Therefore, our findings demonstrate that PDT promotes cholesterol efflux by inducing autophagy, and the autophagy was mediated in part through the ROS/PI3K/Akt/mTOR signaling pathway in THP-1 and peritoneal macrophage-derived foam cells.

Highly sensitive fluorescence sensing of zearalenone using a novel aptasensor based on upconverting nanoparticles.

A facile strategy was successfully developed for the detection of zearalenone (ZEN). In this assay, highly fluorescent upconversion nanoparticles were synthesized and conjugated with the complementary oligonucleotide of ZEN aptamer for use as signal probes. Magnetic nanoparticles immobilized with the ZEN aptamer were assigned as capture probes. The results exhibited that the linear correlation between the decreased luminescence intensity of the signal and the concentration of ZEN was very strong (R2=0.9957) in the range of 0.05-100μg/L. In addition, the limit of detection of the proposed method (0.126μg/kg for corn and 0.007μg/L for beer) was significantly lower than the existing methods. Furthermore, the reliability of the competitive immunoassay format was validated by comparing the results determined in real food samples to those obtained from a commercially available method. Overall, the novel aptasensor have showed great potential for rapid and accurate ZEN determination.

Energy Transfer Probing as the Method for Testing Rare-earth Ions Doped “green” Nanoparticles as Fluorescent Agent for Bioimaging

In spite of tremendous number of papers concerning rare-earth (RE) doped fluorescent nanoparticles (NP) and methods of their synthesis (see, for example, paper in Nature Photonics the problem of fluorescent quenching caused by —OH molecular vibrations is still not raised properly. The reason might be that most of the papers are devoted to the up-conversion fluorescent nanoparticles with the energy of emitted photons in the visible or even in UV spectral ranges. In this case the contribution of the quenching caused by the —OH groups to the overall relaxation rate is not so significant due to very high energy of optical transitions. However, in the near IR spectral range the input of the —OH groups to fluorescence quenching is significant, but until recently there were only few papers, which are raising this issue.