Biocompatible NaYF4:Yb,Er upconversion nanoparticles: Colloidal stability and optical properties

Currently, highly luminescent colloidal upconversion nanoparticles (UCNPs) have expanded an increasing interest of researchers because of their facilitating lability in the biomedical/clinical field. In this study, NaYF₄:Yb,Er UCNPs are prepared by eco-friendly metal complexation-based thermal decomposition method at a lower temperature in aqueous media. The phase structure, crystallinity, phase purity, morphology, colloidal dispersibility, surface structure, surface charge, and optical and luminescent properties were evaluated carefully by X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), energy dispersive x-ray analysis (EDX), Thermogravimetric analysis (TGA), zeta potential, Fourier transform infrared (FTIR), UV/visible and photoluminescent spectroscopic techniques. XRD pattern shows a pure single-phase cubic structure with an average grain size of 30–35 nm. TEM and SEM micrographs exhibited irregularly shaped spherical morphologies, porous surface structures highly aggregated UCNPs with the narrow-size distribution. Positive zeta potential has shown value signifying high absorption in the visible region which indicates particle's good colloidal stability in aqueous media. Under NIR-laser light excitation, the UCNPs emit strong UC emission transitions in the visible region. A broad infrared absorption peak of hydroxyl groups (–OH) in FTIR spectrum and mass loss at a lower temperature in TGA verified the surface functionality of UCNPs, with high colloidal stability, and excellent biocompatibility in aqueous media. In terms of their surface characteristics and high luminescent properties, the NaYF₄:Yb,Er UCNPs could be interestingly applied in tagging of biomolecules, drug delivery, proteins labeling, and therapeutic and thermostats applications.     

Upconversion nanomaterials: a platform for biosensing,theranostic and photoregulation

Upconversion nanoparticles (UCNPs) are a kind of unique optical material, that are able to emit ultraviolet (UV), visible or near infrared (NIR) luminescence upon NIR light excitation. Because of their excellent physic-chemical characters including enormous anti-Stokes spectral shift, high resistance to photobleaching, fairly long luminescent lifetime, excellent chemical stability, sharp emission band, and deep tissue penetration depth, UCNPs have become a useful tool in bioimaging, biosensing, as well as cancer therapy. In particularly, the emissions light from UCNPs can activate photosensitive molecules, which has the potential to realize the regulation of cell behaviors, including cell growth, adhesion and differentiation. This review consequently introduces the principle and achievements of UCNPs in biomedical field to the general readers for promoting both fundamental research and bio-applications of UCNPs. After the brief introduction of the physical mechanism of upconversion luminescence (UCL), we introduce several strategies to enhance the emissions brightness in detail, then discuss various biomedical applications of UCNPs.     

Effects of Surface Modification of Upconversion Nanoparticles on Cellular Uptake and Cytotoxicity

Lanthanide-doped upconversion nanoparticles(UCNPs) are great promising to apply to biomedical imaging and therapy. We prepared NaYF₄:Yb³⁺,Er³⁺ nanoparticles with different surface ligands, i.e., without any ligands(bare), coordinated with 2-aminoethyl dihydrogen phosphate(AEP), polyacrylic acid(PAA) or polyallylamine (PAAm), via a simple two-step ligand exchange of oleic acid capped NaYF₄:Yb³⁺,Er³⁺ nanoparticles. Although the surface modification retained the crystal structure and transimission electron microscope(TEM) size distribution of the nanoparticles, and good dispersibility in aqueous solution and did not significantly change the upconversion luminescence, distinct differences were observed in the surface charge and hydrodynamic diameter. The cellular uptake and cytotoxicity of the nanoparticles were studied on two different cell lines, breast cancer MCF-7 and fibroblast 3T3. Confocal microscopy images demonstrate that PAAm-coordinated UCNPs can enhance the cellular uptake and endocytosis, whereas AEP- and PAA-coordinated UCNPs show a very low level of nonspecific adsorption. Biocompatibility studies based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, however, indicate that PAAm-coordinated UCNPs are more toxic than the other two, and thus need further modifiaction(like PEG coordinating) to improve their biocompatibility. These results are important to the knowledge base required for the biomedical application of the UCNPs.     

Enhanced red emission from GdF3:Yb3+,Er3+ upconversion nanocrystals by Li+ doping and their application for bioimaging

Under 980?nm near-infrared (NIR) excitation, upconversion luminescent (UCL) emission of GdF(3):Yb,Er upconversion nanoparticles (UCNPs) synthesized by a simple and green hydrothermal process can be tuned from yellow to red by varying the concentration of dopant Li(+) ions. A possible mechanism for enhanced red upconverted radiation is proposed. A layer of silica was coated onto the surface of GdF(3):Yb,Er,Li UCNPs to improve their biocompatibility. The silica-coated GdF(3):Yb,Er,Li UCNPs show great advantages in cell labeling and in vivo optical imaging. Moreover, GdF(3) UCNPs also exhibited a positive contrast effect in T(1)-weighted magnetic resonance imaging (MRI). These results suggest that the GdF(3) UCNPs could act as dual-modality biolabels for optical imaging and MRI.     

Luminescent Ink Based on Upconversion of NaYF4:Er,Yb@MA Nanoparticles: Environmental Friendly Synthesis and Structural and Spectroscopic Assessment

NaYF₄:Er,Yb upconversion luminescent nanoparticles (UCNPs) were prepared by hydrothermal methods at 180 °C for 24 h. The X-ray diffraction (XRD) and TEM (transmission electron microscopy) images show that the resulting 60 nm UCNPs possess a hexagonal structure. In this work, maleic anhydride (MA) was grafted on the surface of UCNPs to induce hydrophilic properties. The photoluminescence spectra (PL) show upconversion emissions centered around 545 nm and 660 nm under excitation at 980 nm. The luminescent inks, including UCNPs@MA, polyvinyl alcohol (PVA), deionized water (DI), and ethylene glycol (EG), exhibit suitable properties for screen printing, such as high stability, emission intensity, and tunable dynamic viscosity. The printed patterns with a height of 5 mm and a width of 1.5 mm were clearly observed under the irradiation of a 980 nm laser. Our strategy provides a new route for the controlled synthesis of hydrophilic UCNPs, and shows that the UCNPs@MAs have great potential in applications of anti-counterfeiting packing.     

Versatile synthesis strategy for carboxylic acid-functionalized upconverting nanophosphors as biological labels

Up-converting rare-earth nanophosphors (UCNPs) have great potential to revolutionize biological luminescent labels, but their use has been limited by difficulties in obtaining UCNPs that are biocompatible. To address this problem, we have developed a simple and versatile strategy for converting hydrophobic UCNPs into water-soluble and carboxylic acid-functionalized analogues by directly oxidizing oleic acid ligands with the Lemieux-von Rudloff reagent. This oxidation process has no obvious adverse effects on the morphologies, phases, compositions and luminescent capabilities of UCNPs. Furthermore, as revealed by Fourier transform infrared (FTIR) and NMR results, oleic acid ligands on the surface of UCNPs can be oxidized into azelaic acids (HOOC(CH2)7COOH), which results in the generation of free carboxylic acid groups on the surface. The presence of free carboxylic acid groups not only confers high solubility in water, but also allows further conjugation with biomolecules such as streptavidin. A highly sensitive DNA sensor based on such streptavidin-coupled UCNPs have been prepared, and the demonstrated results suggest that these biocompatible UCNPs have great superiority as luminescent labeling materials for biological applications.     

Sequence‐Dependent DNA Functionalization of Upconversion Nanoparticles and Their Programmable Assemblies

DNA‐modified lanthanide‐doped upconversion nanoparticles (DNA‐UCNPs) that combine the functions of DNA and the optical features of UCNPs have shown great promise in a wide range of fields. However, challenges remain in precisely tethering and orienting the DNA strands on the UCNP surface. Herein, we systematically investigate the sequence dependence of DNAs in their interactions with UCNPs, and reveal that poly‐cytosine (poly‐C) has high affinity for the UCNP surface. A general approach to synthesize monodispersed DNA‐UCNP conjugates is developed using poly‐C‐containing diblock DNA strands. The poly‐C segment of the DNA strand binds to the surfaces of UCNPs and the second segment is oriented perpendicularly on the UCNP surface, making the DNA‐UCNPs highly stable and monodispersed in aqueous solution. The dense layer of DNA on the UCNP surface enables the programmable assembly of UCNPs with other DNA‐functionalized nanoparticles or DNA origamis through hybridization, resulting in the formation of well‐organized complex structures.     

Aptamer-functionalized magnetic nanoparticle-based bioassay for the detection of ochratoxin A using upconversion nanoparticles as labels

A sensitive luminescent bioassay for the detection of ochratoxin A (OTA), a small molecular mycotoxin, was developed using aptamer-conjugated magnetic nanoparticles (MNPs) as the recognition and concentration element and upconversion nanoparticles (UCNPs) as highly sensitive labels. The bioassay system was fabricated by immobilizing aptamer DNA 1 sequence onto the surface of Fe(3)O(4) MNPs, which were implemented to capture and concentrate OTA from bulk samples. The aptamer DNA 1 sequence then hybridized with UCNPs modified with DNA 2 sequence, which could dissociate from DNA 1 and result in a decreased luminescent signal when aptamer DNA 1 recognized and bound to target OTA. Under the optimal conditions, the decreased luminescent intensity (ΔI) is proportional to the concentration of OTA in the range of 1 × 10(-13) to 1 × 10(-9) g mL(-1) with a detection limit of 1 × 10(-13) g mL(-1). The proposed method then was successfully applied to measure OTA in naturally contaminated maize samples and validated by a commercially available enzyme-linked immunosorbent assay (ELISA) method. Benefiting from the magnetic separation and concentration effect of MNPs, the high sensitivity of UCNPs, as well as the selectivity and stability of the aptamer, the present upconversion luminescent bioassay offers a promising approach for the screening of small molecular mycotoxins because it is simple, rapid, highly sensitive, specific, does not require sample pre-concentration and lacks interference from autofluorescence of other biomolecules.     

Novel microwave-assisted solvothermal synthesis of NaYF4:Yb,Er upconversion nanoparticles and their application in cancer cell imaging

This work reports the novel microwave-assisted solvothermal synthesis and structural, topographic, spectroscopic characterization of NaYF(4):Yb,Er upconversion nanoparticles (UCNPs) as well as their application in the labeling of HeLa cells. The nanoparticles were prepared in ethylene glycol, with rare earth acetates as precursor and NH(4)F and NaCl as the fluorine and sodium sources. X-ray diffraction, transmission electron microscopy, and luminescence spectroscopy were applied to characterize the nanoparticles. Experimental results showed that the microwave-assisted solvothermal method is an effective approach to create highly crystalline, strongly luminescent UCNPs at a lower temperature (160 °C) and within a significantly shortened reaction time (only 1 h) compared to the traditional methods. The effect of fluorine source on the optical properties of UCNPs was investigated by using NH(4)F, NH(4)HF(2), NaF, and 1-butyl-3-methylimidazolium tetrafluoroborate (BmimBF(4)) as different fluorine sources; NH(4)F proved to be the best one, making the luminescent intensity increase at least 2 orders of magnitude. The UCNPs with four different colors (green, yellow, orange, and cyan) were successfully obtained. After being modified with amino groups and coupled with CEA-8 antibody, the obtained nanoparticles were successfully applied in the specific fluorescent immunolabeling and imaging of HeLa cells to further verify their function as a marker in immunolabeling.     

Synthesis and Application of Nanohybrids Based on Upconverting Nanoparticles and Polymers

Lanthanide‐doped upconversion nanoparticles (UCNPs) have been an emerging and exciting research field in recent years due to their unique luminescent properties of converting near‐infrared light to shorter wavelength radiation. UCNPs offer excellent prospects in luminescent labeling, displays, bioimaging, bioassays, drug delivery, sensors, and anticounterfeiting applications. Along with the abundant studies and rapid progress in this area, UCNPs are promising to be a new class of luminescent probe owing to their special advantages over the conventional organic dyes and quantum dots. Among them, polymers play an important role to improve properties or endow new function of UCNPs such as for matrix materials, water solubility, linking active targeting molecules, biocompatibility, and stimuli‐responsive behavior. This article briefly reviews the compositions, optical mechanisms, architectures of upconversion nanocrystals and highlights the works on various functional UCNPs/polymer nanohybrids as well as many new interesting fruits in applications.

     

Synthesis and surface modification of ultrasmall monodisperse NaYF4:Yb3+/Tm3+ upconversion nanoparticles

The emerging upconversion nanoparticles (UCNP) have gained substantial consideration in the field of bioanalytical as well as diagnostic applications. Therefore, great progress has been made in the synthesis and surface modification of luminescent UCNPs over the last two decades. In this paper, we have reported monodispersed and high luminescent upconversion nanoparticles NaYF₄: 20%Yb³⁺, 2%Tm³⁺ have been synthesized using a solvothermal method, followed by a coating of the NaYF₄ shell with a thin layer of SiO₂ on the surface to afford the core-shell NaYF₄:Yb³⁺, Tm³⁺@SiO₂ nanoparticles (NP@SiO₂). The prepared nanoparticles were of strong upconversion fluorescent emission intensity, hexagonal phase, and with an average size of about 8 ± 1 nm, which have been characterized by luminescence spectroscopy, powder X-ray diffraction (P-XRD), Dynamic light scattering (DLS), and Transmission electron microscopy (TEM). The results indicate that the NP@SiO₂ can be used for the conjugation of fluorescent probes for various biomolecules and can find applications in cancer cell imaging and disease diagnosis.     

Sequence-Dependent DNA Functionalization of Upconversion Nanoparticles and Their Programmable Assemblies

DNA-modified lanthanide-doped upconversion nanoparticles (DNA-UCNPs) that combine the functions of DNA and the optical features of UCNPs have shown great promise in a wide range of fields. However, challenges remain in precisely tethering and orienting the DNA strands on the UCNP surface. Herein, we systematically investigate the sequence dependence of DNAs in their interactions with UCNPs, and reveal that poly-cytosine (poly-C) has high affinity for the UCNP surface. A general approach to synthesize monodispersed DNA-UCNP conjugates is developed using poly-C-containing diblock DNA strands. The poly-C segment of the DNA strand binds to the surfaces of UCNPs and the second segment is oriented perpendicularly on the UCNP surface, making the DNA-UCNPs highly stable and monodispersed in aqueous solution. The dense layer of DNA on the UCNP surface enables the programmable assembly of UCNPs with other DNA-functionalized nanoparticles or DNA origamis through hybridization, resulting in the formation of well-organized complex structures.     

Upconversion nanophosphors for small-animal imaging

Rare-earth upconversion nanophosphors (UCNPs), when excited by continuous-wave near-infrared light, exhibit a unique narrow photoluminescence with higher energy. Such special upconversion luminescence makes UCNPs promising as bioimaging probes with attractive features, such as no auto-fluorescence from biological samples and a large penetration depth. As a result, UCNPs have emerged as novel imaging agents for small animals. In this critical review, recent reports regarding the synthesis of water-soluble UCNPs and their surface modification and bioconjugation chemistry are summarized. The applications of UCNPs for small-animal imaging, including tumor-targeted imaging, lymphatic imaging, vascular imaging and cell tracking are reviewed in detail. The exploration of UCNPs as multifunctional nanoscale carriers for integrated imaging and therapy is also presented. The biodistribution and toxicology of UCNPs are further described. Finally, we discuss the challenges and opportunities in the development of UCNP-based nanoplatforms for small-animal imaging (276 references).     

核酸适配体功能化的稀土上转换纳米材料在生物检测中的应用

稀土上转换纳米材料可以吸收近红外光并发射出可见光或紫外光,在生物传感领域得到了广泛研究。核酸适配体能高特异性和高亲和性地与靶标物结合,被广泛应用于生物传感、疾病诊断等领域。将稀土上转换纳米材料与核酸适配体结合构建的检测体系,可实现对目标物灵敏、高选择性的检测。本文介绍了近几年核酸适配体功能化的稀土上转换纳米材料在生物小分子、蛋白质、核酸、病原微生物、细胞等方面的应用,并展望了其在分析检测领域的发展前景。     

优化稀土上转换纳米材料发光的方法

稀土上转换纳米材料(Upconversion Nanoparticles,UCNPs)可将近红外光转换为可见光,其发光性能优异、化学性质稳定、激发光能有效避免自荧光,因此在生物医学领域应用广泛。但UCNPs的低发光效率限制了其进一步发展。本文综述了近年来研究较多的几种优化稀土上转换纳米材料发光的方法,主要包括调整基质材料和掺杂离子、过渡金属离子与镧系离子共掺杂、引入协同敏化剂减少热效应、有机染料与UCNPs协同作用以及金属表面等离子体共振增强法等。文中分别论述了上述方法的最新研究进展,并总结了这些方法目前存在的问题,指出上转换发光领域的研发重点:一是着重分析各种优化发光方法的作用机理,提出更加完备清晰的理论体系;二是探索更容易被生物体降解的UCNPs,使其副作用降到最低。     

Blue-emissive upconversion nanoparticles for low-power-excited bioimaging in vivo

Water-soluble upconversion luminescent (UCL) nanoparticles based on triplet-triplet annihilation (TTA) were successfully prepared by coloading sensitizer (octaethylporphyrin Pd complex) and annihilator (9,10-diphenylanthracene) into silica nanoparticles. The upconversion luminescence quantum yield of the nanoparticles can be as high as 4.5% in aqueous solution. As determined by continuous kinetic scan, the nanoparticles have excellent photostability. Such TTA-based upconversion nanoparticles show low cytotoxicity and were successfully used to label living cells with very high signal-to-noise ratio. UCL imaging with the nanoparticles as probe is capable of completely eliminating background fluorescence from either endogenous fluorophores of biological sample or the colabeled fluorescent probe. In particular, such blue-emissive upconversion nanoparticles were successfully applied in lymph node imaging in vivo of living mouse with excellent signal-to-noise ratio (>25), upon low-power density excitation of continuous-wave 532 laser (8.5 mW cm(-2)). Such high-contrast and low-power excited bioimaging in vivo with a blue-emissive upconversion nanoparticle as probe may extend the arsenal of currently available luminescent bioimaging in vitro and in vivo.     

稀土上转换发光纳米材料的应用

稀土上转换发光纳米材料(简称UCNPs)不仅光稳定性强、发射带窄、荧光寿命长、化学稳定性高、潜在生物毒性低,而且采用近红外连续激发光源激发还使其具有较大的光穿透深度、无光闪烁和光漂白、无生物组织自发荧光以及对生物组织几乎无损伤等显著优点,已经成为当前很多领域乃至交叉科学的应用研究热点。由于氟化物基质的UCNPs具有较高的发光效率,本文首先归纳总结了近年来氟化物UCNPs的主要合成及表面改性方法,然后重点综述了近年来UCNPs在免疫分析及生物传感、生物成像、载药、光动力理疗及热致理疗、光导开关和信息存储以及太阳能电池等方面的研究与应用进展。     

The Sol-Gel Process for Nano-Technologies: New Nanocomposites with Interesting Optical and Mechanical Properties

Various nanocomposite systems have been synthesized by sol-gel routes. For this reason, prefabricated nanoparticles (SiO2 sols or boehmite powder) have been dispersed after surface modification in sol-gel-derived organically modified or polymeric ligand matrices. In all cases, a significant effect on dispersibility by surface modification could be observed. After curing, the mechanical or optical properties depend strongly on the dispersion and surface modification. Using these results, composites to be used in chip coupling and as hard coatings on polycarbonate and CR 39 have been developed.     

Upconversion nanoparticle-based fluorescence resonance energy transfer assay for Cr(III) ions in urine

A novel assay of chromium(III) ion based on upconversion fluorescence resonance energy transfer was designed and established. Lysine-capped NaYF₄:Yb/Er upconversion nanoparticles (UCNPs) and dimercaptosuccinic acid-capped gold nanoparticles (AuNPs) were used as the energy donor and acceptor, respectively. They were bound together via electrostatic interaction, resulting in the quenching of the fluorescence of UCNPs by AuNPs. Chromium(III) ions can specifically and strongly interact with dimercaptosuccinic acid that was modified on the surface of AuNPs, leading to the separation of AuNPs from UCNPs and the recovery of fluorescence of UCNPs. The fluorescence recovery of UCNPs showed a good linear response to Cr³⁺ concentration in the range of 2–500 nM with a detection limit of 0.8 nM. This method was further applied to determine the levels of Cr³⁺ in urine. Compared with other fluorescence methods, current method displayed very high sensitivity and signal-to-noise ratio because of the excitation of near-infrared that can eliminate autofluorescence, providing a promising examination of biological samples for the diagnostic purposes.     

Controlled synthesis of uniform and monodisperse upconversion core/mesoporous silica shell nanocomposites for bimodal imaging

Here we report the design and controlled synthesis of monodisperse and precisely size-controllable UCNP@mSiO(2) nanocomposites smaller than 50?nm by directly coating a mesoporous silica shell (mSiO(2)) on upconversion nanocrystals NaYF(4):Tm/Yb/Gd (UCNPs), which can be used as near-infrared fluorescence and magnetic resonance imaging (MRI) agents and a platform for drug delivery as well. Some key steps such as transferring hydrophobic UCNPs to the water phase by using cetyltrimethylammonium bromide (CTAB), removal of the excess amount of CTAB, and temperature-controlled ultrasonication treatment should be adopted and carefully monitored to obtain uniform upconversion core/mesoporous silica shell nanocomposites. The excellent performance of the core-shell-structured nanocomposite in near-infrared fluorescence and magnetic resonance imaging was also demonstrated.