Use Of Upconversion Nanoparticles Research Articles

An aptamer based sulfadimethoxine assay that uses magnetized upconversion nanoparticles

The authors describe an aptamer based method for the determination of the antibiotic sulfadimethoxine (SLF). It is making use of upconversion nanoparticles (UCNPs) that act as an internal fluorophors signals, and of aptamers that can specifically recognize SLF. The UCNPs were deposited on the surface of magnetic nanoparticles (magNPs) functionalized with the aptamer. In the presence of SLF, parts of the UCNPs dissociate from the surface of the magNPs, and this results in decreased fluorescence intensity. The findings were exploited to design a fluorometric assay for SLF that has a 0.11 ng·mL−1 detection limit. The method was successfully applied to the quantification of SLF in spiked samples of perch and catfish. Recoveries range from 80.3% to 92.7%, and RSDs from 2.4% to 3.6%.

Engineering water-tolerant core/shell upconversion nanoparticles for optical temperature sensing.

Luminescence thermometry is a promising approach using upconversion nanoparticles (UCNPs) with a nanoscale regime in biological tissues. UCNPs are superior to conventional fluorescent markers, benefiting from their autofluorescence suppression and deep imaging in tissues. However, they are still limited by poor water solubility and weak upconversion luminescence intensity, especially at a small particle size. Recently, YVO4:Er+3,Yb+3 nanoparticles have shown high efficiency upconversion (UC) luminescence in water at single-particle level and high contrast imaging in biological models. Typically, a 980-nm laser triggers the UC process in the UCNPs, which overlaps with maximum absorption of water molecules that are dominant in biological samples, resulting in biological tissues overheating and possible damaging. Interestingly, neodymium (Nd+3) possesses a large absorption cross section at the water low absorption band (808nm), which can overcome overheating issues. In this Letter, we introduce Nd+3 as a new near-infrared absorber and UC sensitizer into YVO4:Er+3,Yb+3 nanoparticles in a core/shell structure to ensure successive energy transfer between the new UC sensitizer (Nd+3) to the upconverting activator (Er+3). Finally, we synthesized water-tolerant YVO4:Er+3,Yb+3@Nd+3 core/shell nanoparticles (average size 20nm) with strong UC luminescence at a biocompatible excitation wavelength for optical temperature sensing where overheating in water is minimized.

Dental optical tomography with upconversion nanoparticles-a feasibility study.

Upconversion nanoparticles (UCNPs) have the unique ability to emit multiple colors upon excitation by near-infrared (NIR) light. Herein, we investigate the potential use of UCNPs as contrast agents for dental optical tomography, with a focus on monitoring the status of fillings after dental restoration. The potential of performing tomographic imaging using UCNP emission of visible or NIR light is established. This in silico and ex vivo study paves the way toward employing UCNPs as theranostic agents for dental applications.

Increasing electrical conductivity of upconversion materials by in situ binding with graphene

Upconversion nanoparticles (UCNPs) hold promise as near-infrared light converters to enhance the efficiency of solar cells. However, the prevalent use of UCNPs in solar cells is restricted by their poor electrical conductivity and low emission efficiency. Here reduced graphene oxide (rGO)–NaYF4:Yb3+/Er3+ composites are proposed to achieve good electrical conductivity due to the high charge carrier mobility of rGO. Composites of rGO and UCNPs combined by a chemical bond are in situ synthesized by the hydrothermal method, followed by a reduction process. The contact of UCNPs with rGO is proved by SEM, and the binding between the rGO–UCNP composites is confirmed by Fourier transform infrared spectroscopy. The composites are doped into the photoanode of a solar cell. As anticipated, electrochemical impedance spectroscopy confirms the good electrical conductivity of the in situ synthesized rGO–UCNPs. Furthermore, the use of rGO–UCNPs in solar cells enables an enhancement in short-circuit current density and overall efficiency by about 10%. These findings reveal that the combination of UCNPs with rGO opens up new opportunities of extending the use of UCNPs in the area of solar energy harvesting.

LUMINESCENCE DIAGNOSTICS OF TUMORS WITH UPCONVERSION NANOPARTICLES

Background: To improve quality of surgery in oncology, it is necessary to completely remove the tumor, including its metastases, to minimize injury to normal tissues and to reduce duration of an intervention. Modern methods of detection based on radiological computerized tomography and magnetic resonance imaging can identify a tumor after its volume has become big enough, i.e. it contains more than 10 billion cells. Therefore, an improvement of sensitivity and resolution ability of diagnostic tools to identify early stages of malignant neoplasms seems of utmost importance. Aim: To demonstrate the potential of a new class of anti-Stokes luminescence nanoparticles for deep optical imaging with high contrast of malignant tumors. Materials and methods: Upconversion nanoparticles with narrow dispersion and a size of 70 to 80 nm, with a core/shell structure of NaYF4:Yb3+:Tm3+/NaYF4 were used in the study. The nanoparticles have an intensive band of anti-Stokes photoluminescence at a wavelength of 800 nm under irradiation with a wavelength of 975 nm (both wavelengths are within the transparency window for biological tissues). The conversion coefficient of the excitation radiation into the anti-Stokes luminescence was 9%. To increase the time during which nanoparticles can circulate in blood flow of small animals, the nanoparticles were covered by a biocompatible amphiphilic polymer shell. As a tumor model we used Lewis epidermoid carcinoma transfected to mice. Results: We were able to obtain stable water colloids of nanoparticles covered with amphiphilic polymer that could preserve their initial size at least for one month. The use of upconversion nanoparticles with a hydrophilic shell made of intermittent maleic anhydride and octadecene co-polymer with subsequent coating with diglycidyl polyethylene glycol ether allowed for reduction of non-specific reaction of nanoparticles with plasma proteins. In its turn, it resulted in an increased time of their circulation in blood flow of small animals for up to 1 hour. With the Lewis lung carcinoma transfected to mice model we demonstrated аn in-life transportation of upconversion nanoparticles into the tumor with a high degree of localization due to a passive EPR effect. The contrast of luminescent signal in the tumor compared to adjacent tissues was at least 70%. The possibility of visualization of upconverted nanoparticles up to 15 mm of biological tissue was shown. Conclusion: The optical imaging techniques with anti-Stokes photoluminescent markers ensure a high contract real-time detection of tumor tissues that allows for their use for intra-operative diagnostics.

Synthesis and Characteristic of the NaYF4/Fe3O4@SiO2@Tb(DBM)3 · 2H2O/SiO2 Luminomagnetic Microspheres with Core–Shell Structure

The structure and properties of the multifunctional nanoparticles were characterized by X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Photoluminescence spectra and Vibrating sample magnetometer (VSM). The experimental results show that the microsphere has the magnetic core and silica shell bonded with terbium complex. These multifunctional nanoparticles exhibit strong visible emission and up-conversion emission, which is based on the use of up-converting nanoparticles (UCNPs) of the NaYF4:Yb3+, Er3+/Tm3+ type that can be excited with 980 nm laser light to give a green and red luminescence, moreover, nanoparticles possess magnetism with a saturation magnetization of 18.48 emu/g and paramagnetism at room temperature.

A upconversion luminescene biosensor based on dual-signal amplification for the detection of short DNA species of c-erbB-2 oncogene.

High-sensitivity detection of trace amounts of c-erbB-2 oncogene was reported to be equal to or surpass the ability of CA 15-3 for early diagnosis and/or follow-up recurrent screening of breast cancer. Therefore, in the current study, by using upconversion nanoparticles (UCNPs), rare earth-doped NaYF4:Yb3+/Er3+ as the luminescent labels, a upconversion luminescent (UCL) biosensor based on dual-signal amplification of exonuclease III (ExoIII)-assisted target cycles and long-range self-assembly DNA concatamers was developed for the detection of c-erbB-2 oncogene. The proposed biosensor exhibited ultrasensitive detection with limit as low as 40 aM, which may express the potential of being used in trace analysis of c-erbB-2 oncogene and early diagnosis of breast cancer.

Mn(2+)-doped NaYF4:Yb/Er upconversion nanoparticle-based electrochemiluminescent aptasensor for bisphenol A.

A novel aptasensor labeled with Mn(2+)-doped NaYF4:Yb/Er upconversion nanoparticles (NaYF4:Yb,Er/Mn UCNPs) was employed in electrogenerated chemiluminescence (ECL) for the sensitive detection of bisphenol A (BPA). The ECL aptasensor was assembled by immobilizing the thiolated aptamers of BPA covalently on a gold nanoparticle (AuNPs)-modified electrode and pairing with complementary DNA labeled with NaYF4:Yb,Er/Mn UCNPs. The ECL aptasensor can not only rapidly and accurately detect BPA concentrations from 0.05 to 100ng/mL with a detection limit of 0.037ng/mL but also provides a new platform for ECL applications based on the use of upconversion nanoparticles as a promising alternative material. Graphical Abstract The NaYF4:Yb,Er/Mn UCNPs combining with the BPA aptamer serving as recognition elements create a ECL platform for the sensitive detection of bisphenol A. The change in ECL signals induced by aptamer-target interactions was measured and a significant decrease in intensity was found on interaction with BPA in the concentration range of 0.05 to 100 ng/mL.

Near-IR photoactivation using mesoporous silica-coated NaYF4:Yb,Er/Tm upconversion nanoparticles.

Photoactivation is a process in which light is used to 'activate' photolabile therapeutics. As a therapeutic strategy, its advantages are that it is noninvasive and that a high degree of spatial and temporal control is possible. However, conventional photoactivation techniques are hampered by the limited penetration depth of the UV and visible lights to which the photosensitive compounds are responsive. Here we describe a protocol for the use of upconversion nanoparticles (UCNs) as light transducers to convert deeply penetrating near-infrared (NIR) light to UV-visible wavelengths matching that of the absorption spectrum of photosensitive therapeutics. This allows the use of deep-penetrating and biologically friendly NIR light instead of low-penetrating and/or toxic visible or UV lights for photoactivation. In this protocol, we focus on two photoactivation applications: photodynamic therapy (PDT) and photoactivated control of gene expression. We describe how to prepare and characterize the UCNs, as well as how to check their function in biochemical assays and in cells. For both applications, the UCNs are coated with mesoporous silica for easy loading of the therapeutics. For PDT, the UCNs are coated with polyethylene glycol (PEG) for stabilization and folic acid for tumor targeting and then loaded with photosensitizers that would be expected to kill cells by singlet oxygen production; the nanoparticles are injected intravenously. For photoactivated control of gene expression, knockdown of essential tumor genes is achieved using UCNs loaded with caged nucleic acids, which are injected intratumorally. The whole process from nanoparticle synthesis to animal studies takes ∼36 d.

Quench-Shield Ratiometric Upconversion Luminescence Nanoplatform for Biosensing.

Upconversion nanoparticles (UCNPs) possess several unique features, but they suffer from surface quenching effects caused by the interaction between the UCNPs and fluorophore. Thus, the use of UCNPs for target-induced emission changes for biosensing and bioimaging has been challenging. In this work, fluorophore and UCNPs are effectively separated by a silica transition layer with a thickness of about 4 nm to diminish the surface quenching effect of the UCNPs, allowing a universal and efficient luminescence resonance energy transfer (LRET) ratiometric upconversion luminescence nanoplatform for biosensing applications. A pH-sensitive fluorescein derivative and Hg(2+)-sensitive rhodamine B were chosen as fluoroionphores to construct the LRET nanoprobes. Both showed satisfactory target-triggered ratiometric upconversion luminescence responses in both solution and live cells, indicating that this strategy may find wide applications in the design of nanoprobes for various biorelated targets.

A novel and sensitive fluorescence immunoassay for the detection of fluoroquinolones in animal-derived foods using upconversion nanoparticles as labels

A novel fluorescence immunoassay to detect fluoroquinolones in animal-derived foods was developed for the first time by use of upconversion nanoparticles as signal-probe labels. The bioassay system was established by the use of coating-antigen-modified polystyrene particles as immune-sensing probes for separation and anti-norfloxacin monoclonal antibody conjugated with carboxyl-functionalized NaYF4:Yb,Er upconversion nanoparticles which were prepared via a pyrolysis method and a subsequent ligand exchange process as fluorescent-signal probes (emission intensity recorded at 542 nm with excitation at 980 nm). Under optimized conditions, detection of fluoroquinolones was performed easily. The detection limit of this fluorescence immunoassay for norfloxacin, for example, was 10 pg mL(-1), within a wide linear range of 10 pg mL(-1) to 10 ng mL(-1) (R (2) = 0.9959). For specificity analysis, the data obtained indicate this method could be applied in broad-spectrum detection of fluoroquinolones. The recoveries of norfloxacin-spiked animal-derived foods ranged from 82.37 to 132.22 %, with coefficients of variation of 0.24-25.06 %. The extraction procedure was rapid and simple, especially for milk samples, which could be analyzed directly without any pretreatment. In addition, the results obtained with the method were in good agreement with those obtained with commercial ELISA kits. The fluorescence immunoassay was more sensitive, especially with regard to the detection limit in milk samples (0.01 ng mL(-1) for norfloxacin): it was 50-fold more sensitive than commercial ELISA kits (0.5 ng mL(-1) for norfloxacin). The results show the proposed fluorescence immunoassay was facile, sensitive, and interference free, and is an alternative method for the quantitative detection of fluoroquinolone residues in animal-derived foods.

Upconversion nanoparticles as versatile light nanotransducers for photoactivation applications.

Remote activation of photoactivable therapeutic compounds by light provides a high spatial and temporal control for activating the therapeutic agent. However, photoactivable compounds are mostly responsive towards ultraviolet (UV) or visible light radiation that has poor tissue penetration depth besides being unsafe to the body in the case of UV light. Nanoparticles with energy upconversion hold potential in overcoming this limit by using safe and deeply penetrating near-infrared (NIR) light. These upconversion nanoparticles (UCNs) act as versatile nanotransducers as they convert NIR light to light of shorter wavelengths that can be tuned to the NIR, visible or UV colors to suit different activation wavelengths. Their highly unusual optical properties to fluoresce with near-zero photobleaching, photoblinking and background autofluorescence are unique and an added benefit when used simultaneously as optional imaging agents. This article reviews recent advancements in the use of UCNs for photoactivation of therapeutic agents. Specifically, we discuss the use of these UCNs for activation of light-sensitive/photocaged molecules or photosensitizers for photocontrolled-delivery and photodynamic therapy.

Erythrocyte membrane-coated NIR-triggered biomimetic nanovectors with programmed delivery for photodynamic therapy of cancer.

A new type of photodynamic therapy (PDT) agents using upconversion nanoparticles (UCNPs) with incorporated photosensitizers as the inner core and an erythrocyte membrane (RM) decorated with dual targeting moieties as the cloak is developed. Owing to the endogenous nature of RM, the RM-coating endows the PDT agents with perfect biocompatibility and stealth ability to escape from the entrapment by the reticulo-endothelial system (RES). More importantly, owing to the unique nature of erythrocyte as an oxygen carrier in the blood, the RM outer layer of the agents unequivocally facilitates the permeation of ground-state molecular oxygen ((3)O2) and the singlet oxygen ((1)O2) as compared to the previously developed PDT agents with other types of coating. Another salient feature of the as-prepared PDT platform is the decoration of RM with dual targeting moieties for selective recognition of cancer cells and mitochondrial targeting, respectively. The synergistic effect of RM coating and dual-targeting of such feature-packed agents are investigated in tumor-bearing mice and the improved PDT therapeutic efficacy is confirmed, which is the first paradigm where RM-coated NIR-triggered nanovectors with programmed delivery ability is applied in PDT of tumor in vivo.

Aptamer-based fluorescence biosensor for chloramphenicol determination using upconversion nanoparticles

A novel aptamer-based fluorescence biosensor was developed for the detection of chloramphenicol (CAP) using aptamer-conjugated magnetic nanoparticles (MNPs) for both recognition and concentration elements and using upconversion nanoparticles (UCNPs) as highly sensitive signal labels. The bioassay system was fabricated by immobilizing aptamer onto the surface of MNPs, which were employed to capture and concentrate CAP. In the absence of target, MNPs-aptamer hybridizes to its complementary DNA (cDNA) which was modified with UCNPs, form the duplex structure therefore giving a maximum fluorescent signal. Upon CAP addition, the aptamer preferentially bound with CAP and caused the dissociation of some cDNA, liberating some UCNPs-cDNA and leading to a decreased fluorescent signal on the surface of MNPs. Under optimized assay conditions, a wide linear detection range (from 0.01 to 1 ng mL−1) was achieved with a detection limit down to 0.01 ng mL−1. The proposed method then was successfully applied to measure CAP in contaminated milk samples and validated by a commercially available enzyme-linked immunosorbent assay (ELISA) method. Improved by the magnetic separation and concentration effect of MNPs, the high sensitivity of UCNPs and the high affinity of aptamers, the present method performs with both high sensitivity and selectivity for CAP. Besides, this strategy can be applied to detect other antibiotics. Utilization of the proposed biosensor for quantitative determination of antibiotics in food samples may provide significant improvements in quality control of food safety.

Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing.

Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.

Upconversion nanoparticles for ratiometric fluorescence detection of nitrite.

We have developed a selective upconversion switching method for the ratiometric fluorescence detection of nitrite using upconversion nanoparticles (UCNPs) and an efficient nitrite reaction. The green emission (λ(em) = 539 nm) of NaYF4:Yb(3+),Er(3+) nanoparticles can be selectively quenched by the neutral red (NR) dye due to the spectral overlap between the emission at 539 nm and the absorption of NR, while its red emission (λ(em) = 654 nm) remains unchanged. Nitrite reacts specifically and strongly with NR to form diazonium salt and lose the diazonium group, which sharply decreases the absorption of NR. Thus, the green emission of NaYF4:Yb(3+),Er(3+) can be recovered by increasing the amount of nitrite, leading to visible color changes from red to orange-yellow and finally green under excitation at 980 nm. The increase in the ratio of emission intensities (I539/I654) is quantitatively correlated to the concentration of nitrite ions. Moreover, the developed method has been successfully applied to nitrite detection in real samples such as drinking water, natural water and meat foods. In particular, the upconversion sensors can efficiently avoid background optical interference and thus show potential for the detection of nitrite salts in complex samples.

Upconversion nanophosphors for use in bioimaging, therapy, drug delivery and bioassays

Upconversion nanoparticles (UCNPs) represent a new class of fluorophores. Both the excitation and (anti-Stokes) emission wavelengths are in the long wave part of the spectrum so that their luminescence can deeply penetrate tissues and cause low photodamage in biological samples. Their large anti-Stokes shifts, sharp emission bands, zero auto-fluorescence from biological samples and high photostability renders them an ideal kind of fluorescent labels for a variety of analytical formats, for bioimaging in cancer therapy. This review covers the basic mechanisms of up-conversion luminescence, the methods for the synthesis and surface modification of biocompatible UCNPs, and aspects of the in vivo delivery of UCNPs. More specifically, we discuss (a) recent progress regarding UCNPs for multimodal targeted tumor imaging, (b) UCNP-based methods of biological detection and sensing, (c) the use of UCNPs in drug delivery, (d) applications in photodynamic therapy, photothermal therapy and radiotherapy. Finally, we are addressing challenges and opportunities of this quickly emerging field. Contains 362 references.

An ultrasensitive homogeneous aptasensor for kanamycin based on upconversion fluorescence resonance energy transfer

We developed an ultrasensitive fluorescence resonance energy transfer (FRET) aptasensor for kanamycin detection, using upconversion nanoparticles (UCNPs) as the energy donor and graphene as the energy acceptor. Oleic acid modified upconversion nanoparticles were synthesized through a hydrothermal process followed by a ligand exchange with hexanedioic acid. The kanamycin aptamer (5'-NH2-AGATGGGGGTTGAGGCTAAGCCGA-3') was tagged to UCNPs through an EDC–NHS protocol. The π–π stacking interaction between the aptamer and graphene brought UCNPs and graphene in close proximity and hence initiated the FRET process resulting in quenching of UCNPs fluorescence. The addition of kanamycin to the UCNPs–aptamer–graphene complex caused the fluorescence recovery because of the blocking of the energy transfer, which was induced by the conformation change of aptamer into a hairpin structure. A linear calibration was obtained between the fluorescence intensity and the logarithm of kanamycin concentration in the range from 0.01nM to 3nM in aqueous buffer solution, with a detection limit of 9pM. The aptasensor was also applicable in diluted human serum sample with a linear range from 0.03nM to 3nM and a detection limit of 18pM. The aptasensor showed good specificity towards kanamycin without being disturbed by other antibiotics. The ultrahigh sensitivity and pronounced robustness in complicated sample matrix suggested promising prospect of the aptasensor in practical applications.

Fluorescence resonance energy transfer between NaYF4:Yb,Tm upconversion nanoparticles and gold nanorods: Near-infrared responsive biosensor for streptavidin

We represent a fluorescence resonance energy transfer (FRET) system using upconversion nanoparticles (UCNPs) and the gold nanorods (GNRs) as the energy donor–acceptor pair for directly determining streptavidin in near-infrared (NIR) region. NaYF4:Yb,Tm UCNPs, which had a strong emission at 800nm under 980-nm excitation, were adopted as the energy donor. The GNRs, which demonstrated strong surface plasmon absorption around 800nm, were chosen as acceptor to quench the 800nm emissions of the UCNPs. There had the spectral overlap between the emission of the donor nanoparticles (UCNPs) and the absorption of the acceptor nanoparticles (GNRs). This UCNP-based FRET system was then used to determine the amount of streptavidin. In this system, NaYF4:Yb,Tm UCNPs conjugated with biotin, while GNRs conjugated with streptavidin. When added GNRs into UCNPs, the streptavidin were preferred to bind with biotin and decreased spacing between the donor and acceptor NPs. Consequently, FRET occurred and a linear relationship between the luminescence quenching efficiency and the concentration of streptavidin was obtained. Owing to the aforementioned merits of UCNPs as an energy donor and the strong quenching ability of GNRs, satisfactory analytical performances have been acquired.

Sensitive and high resolution subcutaneous fluorescence in vivo imaging using upconversion nanoparticles and microarrays

A sensitive and high resolution small animal in vivo imaging system using upconversion nanoparticles (UNPs) and microarrays was developed. The fluorescence tomography using UNPs could achieve higher precision than that using ordinary fluorophores, which was theoretically explained by the finite element method (FEM). Given the autofluorescence-insensitive property of UNPs, a high subcutaneous detection sensitivity of 0.93 × 10(-4) wt% could be achieved with a UNP volume of ∼10 μL in tissue phantoms. Furthermore, UNP fluorophore microarrays (25, 50 and 100 μm arrays) embedded under mouse skin were prepared for subcutaneous in vivo detection. An optical clearing method was applied to enhance the skin transparency and improve the spatial resolution. The results demonstrated that the optimized system could achieve a spatial resolution of 50 μm for in vivo detection of subcutaneous UNP microarrays. Taken together, we conclude that the proposed system and UNP microarrays could achieve sensitive, high resolution subcutaneous in vivo detection, and have great potential for high throughput detection of tumors and other diseases.