Shell Upconversion Nanoparticles Research Articles

“Integrated diagnosis and treatment” of upconversion nanocomposite hydrogel for osteoarthritis treatment

Osteoarthritis (OA) is a common degenerative joint disease for which there is no definitive treatment. Mesenchymal stem cells (MSCs) can be differentiated into many types of cells such as chondrocytes, which have been used for OA treatment. How to keep the cell viability and promote the chondrogenic differentiation after MSCs transplantation into the knee joint cavityiscrucial. In this study, upconversion nanocomposite hydrogel was developed for integrated diagnosis and treatment of OA. The Er doped core–shell upconversion nanoparticles (UCNPs) were synthesized first and coated on mesoporous silica (UCNP@mSiO2). Then, an H2O2-sensitive thioketal (TK) linker (MAL-PEG-TK-NHS) was attached to the UCNP@mSiO2 surface to link capsular β-cyclodextrin (NH2-β-CD) and black hole quencher (NH2-BHQ3) to form functionalized UCNPs. After loading the drug kartogenin (KGN) that can induce chondrogenic differentiation of MSCs, the UCNP/KGN nanocomposites were mixed with VitroGel to formed the upconversion nanocomposite hydrogel (UCNP/VitroGel). The UCNP/VitroGel could allow MSCs to be implanted well and maintain good survival in vitro. In the presence of hydrogen peroxide (H2O2), the TK bond breakage and triggered release BHQ to recover the fluorescence of UCNPs for ROS detection, and the β-CD also left from the surface of UCNPs to release KGN for inducing the chondrogenic differentiation of MSCs. Thus, the UCNP/VitroGel could detect the ROS after inject into the knee joint cavity for OA diagnosis first via the fluorescence recovery of UCNPs under the 980 nm near-infrared light. And then the KGN release from UCNP/KGN nanocomposites in the environment of OA to induce the chondrogenic differentiation of MSCs for the treatment of OA. This UCNP/VitroGel will be a powerful tool for “integrated diagnosis and treatment” of OA.

A strategy for the accurate detection of glucose in human serum based on the IFE effect of up-transformed nanoparticles

Here, the inner filter effect (IFE) was applied to construct a “turn off” mode up-conversion fluorescence and colorimetric dual-reading detection platform consisting of the chromogenic substance p-phenylenediamine (PPD) and NaYF4:Yb/Er@NaYF4 core–shell up-conversion nanoparticles (UCNPs) for the detection of glucose and hydrogen peroxide (H2O2) with high sensitivity and selectivity. In this strategy, hydrogen peroxide is produced in the process of glucose oxidation by catalyzing glucose oxidase (GOx). PPD is oxidized by H2O2 under the action of horseradish peroxidase (HRP), resulting in the transformation into its oxidation product PPDox, whose absorption peak coincides with the emission peak of UCNP at 540 nm, which can significantly quench the fluorescence of UCNP. The quenching efficiency is related to PPDox production, so the relationship between the glucose content and the fluorescence changes of UCNP can be established to realize the sensitive detection of glucose. UCNPs modified by –COOH and the oxidation product of PPD were negatively charged, which increased the distance between donor and recipient due to electrostatic repulsion. It was not conducive to the occurrence of distance-dependent fluorescence resonance energy transfer (FRET), which was also verified by fluorescence lifetime test. Under the optimal experimental conditions, the linear ranges of hydrogen peroxide and glucose were 2.5 ∼ 50 and 5 ∼ 80 μmol/L with the detection limit (LOD) of 0.32 and 0.83 μmol/L, respectively, which were lower than of some reported approaches. Furthermore, the system could be applied to the detection of glucose in actual serum sample and the results were consistency of commercial glucose meters which indicated that the protocol was reliable and potential applications for clinical diagnosis.

Development of photocatalyst based on NaYF4: Yb, Tm@NaYF4: Yb, Ce/NH2-MIL-101 (Cr): Doping Ce3+ ions to promote the efficient energy transfer between core and shell

Utilization of the whole solar spectrum for the photocatalysis is still a challenge and interesting topic. A series of novel photocatalysts are fabricated by combination of core–shell upconversion nanoparticles NaYF4: Yb, Tm@NaYF4: Yb, Ce (Tm@Ce) with the NH2-MIL-101 (Cr) (NMC) (Tm@Ce/NMC). Tm@Ce/NMC displays the high stability, wide photoresponsive range from UV–Vis to NIR, and excellent photocatalytic activity for decomposition of RhB. With the optimal doping amount of Ce3+ ions and ratio between Tm@Ce and NMC, the degradation of RhB is improved by 1.13, 1.14, and 1.50 times as compared with NaYF4: Yb, Tm/NMC (Tm@NMC), under the simulated solar light, UV + Vis, and NIR, respectively. The enhanced photocatalytic activity of Tm@Ce/NMC is mainly attributed to the efficient energy transfer between core and shell by the doping Ce3+ ions along with the distinct charge separation and suppressed recombination. By the controlled synthesis, the NaYF4: Yb, Tm (YT) nanoparticle is developed with the similar size as the Tm@Ce to further testify the effect of doping Ce3+ ions and exclude the influence of the increased size. The photocatalytic activity of YT/NMC is the less than that of Tm@Ce/NMC, which is almost the same with that of Tm/NMC. It suggests that to merely increase the size of upconversion nanoparticles is not the judicious choice for enhancement of the photocatalytic activity. On the basis of the trapping experiments and other spectra properties, the possible photocatalytic mechanism is conjectured, which is helpful to refine the structure design with the ultimate aim to get the robust photocatalyst.

Near-Infrared Light-Triggered Drug Release from Ultraviolet- and Redox-Responsive Polymersome Encapsulated with Core-Shell Upconversion Nanoparticles for Cancer Therapy.

Combining upconversion nanoparticles (UCNPs) and UV-sensitive polymers to form a smart drug delivery system (DDS) is a promising strategy to circumvent drawbacks of direct UV excitation in clinical applications. This study tuned up core-shell UCNPs with a shell thickness of 6 nm and emission wavelength falling in the ultraviolet region at 350 nm under near-infrared (NIR) light irradiation at 980 nm. An amphiphilic block copolymer with UV-responsive o-nitrobenzyl ester (ONB) next to a glutathione (GSH)-responsive disulfide linkage was synthesized and formulated into a polymersome. Core-shell UCNPs and doxorubicin (DOX) were simultaneously encapsulated into the polymersome during double emulsion for DDS. The combination of NIR light-inducing photolysis of the ONB linkage and GSH cleaving the disulfide linkage enhanced DOX release for chemotherapy. From in vitro evaluation, the polymersome alone was nontoxic against three lung cancer cell lines, but the one loaded with core-shell UCNPs and DOX showed severe cell-killing effect under the assistance of a 980 nm diode laser. In vivo study in A549 tumor-bearing mice verified significant inhibition of tumor growth in mice treated with the polymersome containing core-shell UCNPs and DOX under 980 nm diode laser irradiation as compared with those without laser irradiation and those treated with free DOX. This intriguing nanomedicine of well-defined structures responsive to NIR light and reducing agents offers potential for smart DDS applications.

Fabrication of multicolor Janus microbeads based on photonic crystals and upconversion nanoparticles

In this study, a facile method to fabricate Janus microbeads based on photonic crystals and upconversion nanoparticles is designed. The Janus microbeads can be reversed under magnetic response and generate upconversion fluorescence under near-infrared light. Three kinds of core–shell upconversion nanoparticles (UCNPs) are prepared by the solvothermal method and are mixed with Fe3O4 nanoparticles and different sizes of colloidal spheres. The Janus microbeads are assembled according to the hydrophilic property of the mixture and the hydrophobic property of substrates. The upper parts of the Janus microbeads are photonic crystals assembled with colloidal spheres, and the other parts are Fe3O4. Meanwhile, UCNPs are distributed inside the Janus microbeads. Furthermore, the Janus microbeads are prepared into different lattice patterns using special templates. In the lattice patterns, the structural colors of Janus microbeads can be displayed and disappeared by magnetic field inversion, and under external NIR irradiation, Janus microbeads can generate upconversion fluorescence to achieve multiple color display. The Janus microbeads are also applied to both sides of the bank card, and various reading information methods are designed according to different response modes, which have important applications in pattern display, response materials, and anti-counterfeiting.

High Color-Purity Red, Green, and Blue-Emissive Core-Shell Upconversion Nanoparticles Using Ternary Near-Infrared Quadrature Excitations.

Development of multicolor-emitting upconversion nanoparticles (UCNPs) is of significant importance for applications in optical encoding, anti-counterfeiting, display, and bioimaging. However, realizing the orthogonal three-primary color (TPC) upconversion luminescence in a single nanoparticle remains a huge challenge. Herein, we have rationally designed core-multishell-structured NaYF4 UCNPs through regulating the dopant concentration, composition of luminescent layers, and shell position and thickness, which are capable of emitting red, green, and blue luminescence with high color purity in response to ternary near-infrared quadrature excitations (1560/808/980 nm). Moreover, their high color purity is well retained with varying excitation power densities. This orthogonal TPC emissions property of such UCNPs endows them with great promise in the field of security. As a proof-of-concept, we have demonstrated the feasibility of combining such UCNPs with MnO2 nanosheets for information encryption and decryption. This work not only offers a new way to achieve TPC upconversion luminescence at a single nanoparticle level but also broadens the scope of application for security protection.

Blue/red ratiometric pH sensors without background signals based on 808 nm-excited core–triple shell up-conversion nanoparticles

A pH sensor based on CTS UCNPs exhibits ratiometric responses from pH 4 to 7 according to blue/red luminescence intensity ratios under 808 nm excitation.

Linear Coassembly of Upconversion and Perovskite Nanoparticles: Sensitized Upconversion Emission of Perovskites by Lanthanide‐Doped Nanoparticles

AbstractSensitized emission of lead halide perovskite nanoparticles (LHPNPs) can be achieved by near‐infrared (NIR) excitation of nearby lanthanide‐doped upconversion nanoparticles (UCNPs) by using a low‐cost diode laser. Here, the first preparation of linear assemblies of core and core–shell NPs, as well as linear coassemblies of LHPNPs and UCNPs, within an open peapod‐like lead sulfate shell are reported. UCNPs with a NaYF4 matrix doped with ytterbium and thulium or erbium, and with an inert shell of NaYF4 in the case of core‐shell, and all‐inorganic CsPbX3 NPs (X = halide) are chosen for these studies. Interestingly, the lead sulfate shell enhances the luminescence of the core/core– shell UCNPs in the polymers by ≈20‐fold and it also plays a role in the efficiency of the sensitized emission of the LHPNPs under NIR excitation of the UCNP‐LHPNP copolymers, as well as in the chemical stability of the LHPNPs in contact with water. The (co)polymers are prepared as colloids and deposited as solid films on a glass substrate. The lifetime of the sensitized LHP emission and the efficiency of the process wholly depends on the irradiance and on the sample state. These copolymers are promising candidates for the manufacture of photonic devices.

Low Toxicity, High Resolution, and Red Tissue Imaging in the Vivo of Yb/Tm/GZO@SiO2 Core-Shell Upconversion Nanoparticles.

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted great attention in bioimaging applications. However, the stability and resolution of bioimaging based on UCNPs should be further improved. Herein, we synthesized SiO2-coated Ga(III)-doped ZnO (GZO) with lanthanide ion Yb(III) and Tm(III) (Yb/Tm/GZO@SiO2) UCNPs, which realized red fluorescence imaging in heart tissue. With increasing injection concentrations of Yb/Tm/GZO@SiO2 (1–10 mg/kg), the red fluorescence imaging intensity of heart tissue gradually increased. Moreover, the experimental results of toxicity in vitro and histological assessments of representative organs in vivo were studied, indicating that Yb/Tm/GZO@SiO2 UCNPs had low biological toxicity. These results proved that Yb/Tm/GZO@SiO2 can be used as a probe for fluorescence imaging in vivo.

Atomic-Scale Structural Analysis of Homoepitaxial LaF3:Yb,Tm Core–Shell Upconversion Nanoparticles Synthesized through a Microwave Route

Core–shell upconversion nanoparticles (UCNPs) have been intensely studied and are anticipated to affect fields including solar cells and imaging, sensing, and biomedical applications where both opt...

An efficient NIR-to-NIR signal-based LRET system for homogeneous competitive immunoassay

Upconversion nanoparticles (UCNPs) are promising materials for biological applications based on luminescence resonance energy transfer (LRET). In contrast to classical RET donors such as quantum dots, gold nanoparticles, UCNPs can emit near-infrared (NIR) upon the NIR irradiation, which provides enhanced signal-to-noise due to strong penetration and low autofluorescence in the NIR region known as the diagnostic window. Here we report the first efficient NIR-to-NIR signal-based LRET system for the detection of progesterone, chosen as a proof-of-concept target, via homogeneous competitive immunoassay. To enhance the efficiency of LRET, we constructed inert-core/active-shell/inert-ultrathin shell UCNPs (NaYF4@NaYF4:Yb,Tm@NaYF4) as an LRET donor and a compact progesterone/horseradish peroxidase/IRdyeQC-1 (P-HRP-dyes) complex as an LRET acceptor. The designed donor and acceptor showed significantly improved LRET efficiencies (95% and 85% for donor and acceptor, respectively) compared with conventional donor and acceptor (70% and 50%, respectively). Using the developed NIR-to-NIR LRET system, progesterone was successfully detected with a background-free signal and low limit of detection (1.36 pg/ml in ten-fold diluted human serum). We believe that the efficient NIR-to-NIR signal-based LRET system developed here has potential as a simple probe for homogeneous competitive immunoassay, with the ability to rapidly detect biomarkers.

Accurate Control of Core–Shell Upconversion Nanoparticles through Anisotropic Strain Engineering

AbstractThe effect of anisotropic interfacial strain on epitaxial growth and optical emission of sodium rare‐earth fluoride core–shell nanoparticles is investigated. A variety of sodium rare‐earth fluoride shells are grown on hexagonal‐phase NaYF4:Yb/Er core for providing anisotropic tuning of interfacial strains. Using high‐resolution transmission electron microscopy and X‐ray diffraction characterizations, the correlations between the epitaxial habits and the interfacial strains are quantitatively addressed. Furthermore, the growth affinity is tuned by controlling precursor concentration in conjunction with Ca2+ doping, which results in accurate regulation of the anisotropic growth. The lattice strain resulting from mismatched epitaxy is found to enhance luminescence response of the nanoparticles to temperature change.

Biosensors: NIR Biosensing of Neurotransmitters in Stem Cell‐Derived Neural Interface Using Advanced Core–Shell Upconversion Nanoparticles (Adv. Mater. 14/2019)

In article number 1806991, Ki-Bum Lee and co-workers describe NIR-based biosensing of neurotransmitters in stem-cell-derived neural interfaces using core–shell upconversion nanoparticles (UCNPs), which presents a unique tool for investigating the single-cell mechanisms associated with dopamine, or other neurotransmitters, and their roles in neurological processes.

Steady State Luminescence Enhancement in Plasmon Coupled Core/Shell Upconversion Nanoparticles

AbstractPlasmon enhanced upconversion luminescence has been deeply investigated and finds extensive applications from fluorescent sensors to cancer therapy. Here, the steady state luminescence enhancement is shown in plasmonic substrate coupled upconversion nanoparticles (UCNPs). The plasmonic Au‐nanohole‐nanoplate bilayer arrays (PABAs) are designed for generating full‐covered local field which couple both the excitation and the emission field of core/shell UCNPs. By tuning the coupling distance through a 3 nm thick inert shielding shell on upconversion nanoparticles, the plasmon enhanced upconversion luminescence enhancement is found independent on excitation power. This effect will greatly facilitate the applications of plasmon enhanced upconversion nanoparticles as biosensors even under extremely weak excitation. E.g., PABA‐supported core/inert–shell UCNPs are employed as a fluorescent sensor for detecting acetic acid gas, and a linear relationship between upconversion luminescent intensity and acetic acid concentration can be obtained as expected, accompanied by a detection limit of 81 nmol mL−1, which is one order of magnitude lower than the best level ever reported.

High Nd(III)-Sensitizer Concentrations for 800 nm Wavelength Excitation Using Isotropic Core–Shell Upconversion Nanoparticles

Upconverting nanoparticles (UCNPs) are potentially useful for biological applications, if they are capable of high-intensity emission. This requires the highest absorption efficiencies of wavelengt...

NIR Biosensing of Neurotransmitters in Stem Cell-Derived Neural Interface Using Advanced Core-Shell Upconversion Nanoparticles.

Nondestructive neurotransmitter detection and real-time monitoring of stem cell differentiation are both of great significance in the field of neurodegenerative disease and regenerative medicine. Although luminescent biosensing nanoprobes have been developed to address this need, they have intrinsic limitations such as autofluorescence, scattering, and phototoxicity. Upconversion nanoparticles (UCNPs) have gained increasing attention for various biomedical applications due to their high photostability, low auto-fluorescent background, and deep tissue penetration; however, UCNPs also suffer from low emission intensities due to undesirable energy migration pathways. To address the aforementioned issue, a single-crystal core-shell-shell "sandwich" structured UCNP is developed that is designed to minimize deleterious energy back-transfer to yield bright visible emissions using low power density excitations. These UCNPs show a remarkable enhancement of luminescent output relative to conventional β-NaYF4:Yb,Er codoped UCNPs and β-NaYF4:Yb,Er@NaYF4:Yb "active shell" alike. Moreover, this advanced core-shell-shell UCNP is subsequently used to develop a highly sensitive biosensor for the ultrasensitive detection of dopamine released from stem cell-derived dopaminergic-neurons. Given the challenges of in situ detection of neurotransmitters, the developed NIR-based biosensing of neurotransmitters in stem cell-derived neural interfaces present a unique tool for investigating single-cell mechanisms associated with dopamine, or other neurotransmitters, and their roles in neurological processes.

Enhanced upconversion luminescence intensity of core–shell NaYF4 nanocrystals guided by morphological control

How to further increase the upconversion luminescence (UCL) efficiency of core–shell upconversion nanoparticles (UCNPs) is highly desirable for their photoelectric and bio-logical applications. Herein, a novel but facile strategy is proposed to substantially enhance the UCL intensity of NaYF4 based core–shell UCNPs by morphological control. The morphologies of core–shell UCNPs can be optimized from rod-like to spherical like by changing the ratio of oleic acid (OA) to 1-octadecene (ODE) during the shell growth process with other reaction conditions constant. The mechanism of shape control is further investigated based on the competitive absorption between OA molecules and lanthanide ions (Y3+, Yb3+, Er3+ or Tm3+) onto the different crystal axes (a, b and c) to guide their shell growth speed. The absolute quantum yields were up to 2.7% and 1.8% for spherical and rod like core–shell UCNPs under excitation of 980 nm laser (power density of 1.6 W cm−2), respectively. Moreover, the UCL intensity and effective lifetime (τeff) of Er3+ emission at 541 nm of spherical like core–shell UCNPs increased by 11.7 and 1.82 folds than rod like core–shell UCNPs. Therefore, our designed novel strategy can greatly improve the UCL efficiency of core–shell UCNPs and promote their development in diverse applications.

Sandwich DNA Hybridization Fluorescence Resonance Energy-Transfer Strategy for miR-122 Detection by Core-Shell Upconversion Nanoparticles.

An upconversion nanoparticle (UCNP)-based fluorescence resonance energy-transfer (FRET) strategy is normally restricted by the complicated preparations, low energy-transfer efficiency, and the challenge on improving specificity. Herein, simple DNA-functionalized UCNPs were designed as energy donors for constructing a FRET-based probe to detect the liver-specific microRNA 122 (miR-122). To improve FRET efficiency, UCNPs were constructed with confined core-shell structures, in which emitting ions were precisely located in the thin shell to make them close enough to external energy acceptors. Subsequently, capture DNA was simply functionalized on the outer surface of UCNPs based on ligand exchange that contributed to shortening the energy-transfer distance without extra modification. To gain high specificity, the donor-to-acceptor distance of FRET was controlled by a sandwich DNA hybridization structure using two shorter DNAs with designed complementary sequences (capture DNA and dye-labeled report DNA) to capture the longer target of miR-122. Therefore, the sensitive detection of miR-122 was achieved based on the decreased signals of UCNPs and the increased signals of the dye labeled on reported DNA. With good biocompatibility, this method has been further applied to cancer cell imaging and in vivo imaging, which opened up a new avenue to the sensitive detection and imaging of microRNA in biological systems.

Core-Shell-Shell Upconversion Nanoparticles with Enhanced Emission for Wireless Optogenetic Inhibition.

Recent advances in upconversion technology have enabled optogenetic neural stimulation using remotely applied optical signals, but limited success has been demonstrated for neural inhibition by using this method, primarily due to the much higher optical power and more red-shifted excitation spectrum that are required to work with the appropriate inhibitory opsin proteins. To overcome these limitations, core-shell-shell upconversion nanoparticles (UCNPs) with a hexagonal phase are synthesized to optimize the doping contents of ytterbium ions (Yb3+) and to mitigate Yb-associated concentration quenching. Such UCNPs' emission contains an almost three-fold enhanced peak around 540-570 nm, matching the excitation spectrum of a commonly used inhibitory opsin protein, halorhodopsin. The enhanced UCNPs are utilized as optical transducers to develop a fully implantable upconversion-based device for in vivo tetherless optogenetic inhibition, which is actuated by near-infrared (NIR) light irradiation without any electronics. When the device is implanted into targeted sites deep in the rat brain, the electrical activity of the neurons is reliably inhibited with NIR irradiation and restores to normal level upon switching off the NIR light. The system is further used to perform tetherless unilateral inhibition of the secondary motor cortex in behaving mice, achieving control of their motor functions. This study provides an important and useful supplement to the upconversion-based optogenetic toolset, which is beneficial for both basic and translational neuroscience investigations.

Enhanced NIR-I emission from water-dispersible NIR-II dye-sensitized core/active shell upconverting nanoparticles

Water-dispersible NIR-II dye (IR-1061) sensitized core/active shell upconversion nanoparticles (800 nm emission of Tm3+ ion).