Structured Upconversion Nanoparticles Research Articles

Simple design of upconversion nanoparticles-based aptasensor integrated microfluidic chip for ultra-sensitive detection of bisphenol A in aquatic products

Bisphenol A (BPA) is an endocrine disrupting chemical having estrogenic properties that can enter the body through leaking from food containers or the food chain. An upconversion nanoparticle-based aptasensor integrated with microfluidic chip was simply designed to achieve the determination of BPA in foodstuff. Core-shell structured upconversion nanoparticles with 6.41-fold luminescence enhancement were used as fluorescence donors and gold nanoparticles as fluorescence acceptors to construct fluorescence resonance energy transfer (FRET) system. The BPA aptamer serves as a link between the building of the FRET system and the BPA-specific recognition component. The fishbone-structured microfluidic chip only needs 0.5 μL sample solution and 4 min to determine the presence of BPA. The proposed method has good linearity for BPA in the range of 0.02–100 ng/mL with calibration curve of y = 0.0918x + 0.6477 and limit of detection of 0.014 ng/mL. It is tremendously competitive to perform on-chip analysis that enables microsampling and rapid determination.

Unraveling the Growth Process of Core–Shell Structured Upconversion Nanoparticles: Implications for Color Tuning of Upconversion Luminescence

The core–shell strategy has been routinely employed to improve emissive properties of upconversion nanoparticles (UCNPs). However, the underlying process of forming the core–shell structure still remains largely unexplored. In this work, we have performed a time-course study on the growth process of NaErF4@NaYF4 core–shell UCNPs to track time-dependent variations in size, phase, elemental distribution, and luminescence properties throughout the whole synthesis process. Our results show that the formation of core–shell UCNPs includes three major stages: formation of α-phase shell precursors, transition of the α-phase to β-phase, and seed-mediated growth. Among these stages, the first two mainly occur in the early stage of the growth process, while the last one dominates the subsequent process. During the seed-mediated growth process, the elemental distribution of the core–shell nanostructure is observed to change after a short time of reaching the reaction temperature and it continues throughout the rest of the growth process. Most importantly, the emissive properties also showed time-dependent variations, which were attributed to the activation of different optical pathways due to different shell thicknesses over time. This study is believed to provide fundamental insights into the growth mechanism of core–shell UCNPs, which can also be potentially applied for tuning the luminescence of other core–shell luminescent nanostructures.

Upconversion nanoparticle-based aptasensor for rapid and ultrasensitive detection of Staphylococcus aureus by low-speed centrifugation.

Opportunistic foodborne pathogens such as Staphylococcus aureus (S. aureus) can cause a wide variety of threats to public health. There is an urgent clinical need for a fast, simple, low-cost, and sensitive method. Here, we designed a fluorescence-based aptamer biosensor (aptasensor) for S. aureus detection using core-shell structured upconversion nanoparticles (CS-UCNPs) as a beacon. A S. aureus-specific aptamer was modified on the surface of CS-UCNPs for binding pathogens. The S. aureus bound to CS-UCNPs can then be isolated from the detection system by simple low-speed centrifugation. Thus, an aptasensor was successfully established for the detection of S. aureus. The fluorescence intensity of CS-UCNPs correlated with the concentration of S. aureus within the range of 6.36 × 102 to 6.36 × 108 CFU mL-1, resulting in the detected limit of S. aureus being 60 CFU mL-1. The aptasensor performed well in real food samples (milk) with a detection limit of 146 CFU mL-1 for S. aureus. Furthermore, we applied our aptasensor in chicken muscles for S. aureus detection, and compared it with the plate count gold standard method. There was no significant difference between our aptasensor and the plate count method within the detected limit, while the time for the aptasensor (0.58 h) was shorter than that of the plate count method (3-4 d). Therefore, we succeeded in the design of a simple, sensitive and fast CS-UCNPs aptasensor for S. aureus detection. This aptasensor system would have the potential for the detection of a wide range of bacterial species by switching the corresponding aptamer.

Multi-shell structured upconversion nanocarriers that combine IDO inhibitor-induced immunotherapy with NIR-triggered photodynamic therapy for deep tumors.

Combination therapies for cancer have attracted substantial research interest as an emerging treatment strategy that can reduce the chance of cancer resistance to chemotherapy and deal effectively with cancer cell heterogeneity. In this study, we designed novel nanocarriers that combine immunotherapy, which attacks tumors by stimulating the immune system, with photodynamic therapy (PDT), a non-invasive phototherapy that can selectively destroy only cancer cells. Multi-shell structured upconversion nanoparticles (MSUCNs) with good photoluminescence (PL) strength were synthesized for a combination therapy of near-infrared (NIR) light-induced PDT and immunotherapy using a specific immune checkpoint inhibitor. By optimizing the doping content of ytterbium ions (Yb3+) and forming a multi-shell structure, MSUCNs able to emit light at multiple wavelengths with the PL efficiency improved by 260-380 times compared to core particles were synthesized. Then, the surfaces of the MSUCNs were modified with folic acid (FA) as a tumor-targeting ligand, Ce6 as a photosensitizer (PS), and 1-methyl-tryptophan (1MT) as an indoleamine 2,3-dioxygenase (IDO) inhibitor. The FA-, Ce6-, and 1MT-conjugated MSUCNs (F-MSUCN3-Ce6/1MT) exhibited targeted cellular uptake by active targeting against HeLa cells, which are FA receptor-positive cancer cells. Upon irradiation with NIR at 808 nm, the F-MSUCN3-Ce6/1MT nanocarriers produced reactive oxygen species, which caused apoptosis of the cancer cells, and activated CD8+ T cells, which enhanced the immune response by binding with immune checkpoint inhibitory proteins and blocking the IDO pathway. Therefore, these F-MSUCN3-Ce6/1MT nanocarriers could be potential candidate materials for synergistic anticancer therapy that combines IDO inhibitor-based immunotherapy with enhanced NIR-triggered PDT.

Preparation of Multishell-Structured NaYF4:Yb,Tm,Nd@NaYF4:Yb,Nd@SiO2@ZnO Nanospheres with Effective NIR-Induced Photocatalytic Activity

The multishell-structured NaYF4:Yb,Tm,Nd@NaYF4:Yb,Nd@SiO2@ZnO nanospheres were synthesized for the first time by combining active-core/active-shell structured upconversion nanoparticles (UCNPs) with ZnO semiconductor. The composite nanospheres can be used as an efficient NIR-induced photocatalyst. Design of core/shell structure for the lanthanide-doped UCNPs (NaYF4:Yb,Tm,Nd@NaYF4:Yb,Nd) greatly improved their upconversion luminescence (UCL) efficiency which was attributed to the increase of NIR absorption at 808 nm based on Nd3+/Yb3+ cascade-sensitized UC process and the efficient energy migration from active-shell to active-core. The composite photocatalyst used the enhanced NIR-to-UV upconverted light from UCNPs to realize dye photodegradation and photosterilization. On the basis of the results of the scavenger test, we confirm that the hydroxyl radicals (•OH) were considered as the main reactive species produced in the charge transfer and played a key role in the photocatalytic reaction process, while the superoxide radicals (•O2–) and holes (h+) as secondary active species also participated in the reaction. As measured by MTT assay, the composite photocatalyst exhibited low cytotoxicity for cells. The possible working mechanism can help us to improve the design and photochemical properties of the multishell-structured photocatalyst with NIR light response.

Holographic polymer nanocomposites with both high diffraction efficiency and bright upconversion emission by incorporating liquid crystals and core-shell structured upconversion nanoparticles

Holographic polymer nanocomposites with upconversion photoluminescence functions have drawn extensive attention. Yet, it still remains challenging to boost the upconversion emission intensity while maintaining a high diffraction efficiency. Herein, we demonstrate a viable approach to fabricating holographic polymer nanocomposites with both high diffraction efficiency and bright upconversion emission by enriching the core-shell structured upconversion nanoparticles (UCNPs) into the constructive regions while enriching the liquid crystal into the destructive regions during photopolymerization. It is found that the mass ratio of oleic acid to H2O (e.g., 2.41–7.65) on the surface of UCNPs plays a critical role to achieve the attractive holographic polymer nanocomposites. Colored holographic images identifiable to the public under room light with four encrypted upconversion emission states (e.g., none, blue, yellow-green and red) are achieved. Moreover, the holographic images are able to show distinct colors at different viewing angles and can be switched by electric fields, showing unclonable features for advanced anti-counterfeiting applications.

Construction of a Dual Drug Carrier on the Basis of Hollow Structured Upconversion Nanoparticles for pH‐Responsive Drug Delivery and UCL/MRI Dual Mode Imaging

AbstractA series of Gd3+ doping hollow upconversion nanoparticles NaYF4:Yb,Gd,Tm (h‐UNCP) are prepared successfully. The hollow NaYF4:Yb,Gd,Tm possess excellent upconversion luminescence (UCL) and large longitudinal relativity (r1 = 128.3 mm−1 s−1), which can be potentially used for UCL/magnetic resonance imaging (MRI) dual mode imaging. On the basis of the optimal h‐UCNP, doxorubicin hydrochloride (DOX) and methotrexate (MTX) are used as drug models to prepare a dual drug carrier. After the encapsulation of DOX on the h‐UCNP, chitosan (CS) is further wrapped and then used to load MTX to obtain a dual drug carrier h‐UCNPs/DOX/CS/MTX. The pH responsive release of DOX and MTX is discussed. The MTX release climbs from 33% to 100% by regulating the pH from 5.8 to 7.4. The DOX release is different at different pH conditions. The synergistic effect of DOX and MTX on the cancer cells is confirmed by cell viability. The h‐UCNPs/DOX/CS/MTX are tracked by cells UCL imaging and vivo MRI imaging. The excellent performance of UCL imaging and positive MRI images demonstrates that h‐UCNPs/DOX/CS/MTX can be used for UCL/MRI dual mode imaging. All the results show the potential application of h‐UCNPs/DOX/CS/MTX in pH responsive release and UCL/MRI dual imaging.

Mass production of poly(ethylene glycol) monooleate-modified core-shell structured upconversion nanoparticles for bio-imaging and photodynamic therapy

Developing robust and high-efficient synthesis approaches has significant importance for the expanded applications of upconversion nanoparticles (UCNPs). Here, we report a high-throughput synthesis strategy to fabricate water-dispersible core-shell structured UCNPs. Firstly, we successfully obtain more than 10 grams core UCNPs with high quality from one-pot reaction using liquid rare-earth precursors. Afterwards, different core-shell structured UCNPs are fabricated by successive layer-by-layer strategy to get enhanced fluorescence property. Finally, the hydrophobic UCNPs are modified with poly(ethylene glycol) monooleate (PEG-OA) though a novel physical grinding method. On the basis of mass-production, we use the as-prepared PEG-UCNPs to construct an 808-nm stimuli photodynamic therapy agent, and apply them in cancer therapy and bio-imaging.

Honeycomb-Satellite Structured pH/H2O2-Responsive Degradable Nanoplatform for Efficient Photodynamic Therapy and Multimodal Imaging.

The oxygen-deprived environment of a solid tumor is still great restriction in achieving an efficient photodynamic therapy (PDT). In this work, we developed a smart pH-controllable and H2O2-responsive nanoplatform with degradable property, which was based on honeycomb manganese oxide (hMnO2) nanospheres loaded with Ce6-sensitized core-shell-shell structured up-conversion nanoparticles (NaGdF4:Yb/Er,Tm@NaGdF4:Yb@NaNdF4:Yb) (abbreviated as hMUC). In the system, the speedy breakup of the as-prepared hMnO2 nanostructures results in release of loaded Ce6-sensitized UCNPs under the condition of H2O2 in acid solution. When exposed to tissue-penetrable 808 nm laser, up-conversion nanoparticles (UCNPs) emit higher-energy visible photons which would be absorbed by Ce6 to yield cytotoxic reactive oxygen species (ROS), thus triggering PDT treatment naturally. Moreover, the in vitro and in vivo experiments demonstrate that hMUC sample with the honeycomb-satellite structure can serve as multimodal bioimaging contrast agent for self-enhanced upconversion luminescence (UCL), magnetic resonance imaging (MRI) and computed tomography (CT) imaging, indicating that the as-prepared hMUC could be used in imaging-guided diagnosis and treatment, which has a potential application in the PDT treatment of tumor.

From UV to Near‐Infrared Light‐Responsive Metal–Organic Framework Composites: Plasmon and Upconversion Enhanced Photocatalysis

The exploitation of photocatalysts that harvest solar spectrum as broad as possible remains a high-priority target yet grand challenge. In this work, for the first time, metal-organic framework (MOF) composites are rationally fabricated to achieve broadband spectral response from UV to near-infrared (NIR) region. In the core-shell structured upconversion nanoparticles (UCNPs)-Pt@MOF/Au composites, the MOF is responsive to UV and a bit visible light, the plasmonic Au nanoparticles (NPs) accept visible light, whereas the UCNPs absorb NIR light to emit UV and visible light that are harvested by the MOF and Au once again. Moreover, the MOF not only facilitates the generation of "bare and clean" Au NPs on its surface and realizes the spatial separation for the Au and Pt NPs, but also provides necessary access for catalytic substrates/products to Pt active sites. As a result, the optimized composite exhibits excellent photocatalytic hydrogen production activity (280 µmol g-1 h-1 ) under simulated solar light, and the involved mechanism of photocatalytic H2 production under UV, visible, and NIR irradiation is elucidated. Reportedly, this is an extremely rare study on photocatalytic H2 production by light harvesting in all UV, visible, and NIR regions.

Multifunctional Theranostics for Dual-Modal Photodynamic Synergistic Therapy via Stepwise Water Splitting.

Combined therapy using multiple approaches has been demonstrated to be a promising route for cancer therapy. To achieve enhanced antiproliferation efficacy under hypoxic condition, here we report a novel hybrid system by integrating dual-model photodynamic therapies (dual-PDT) in one system. First, we attached core-shell structured up-conversion nanoparticles (UCNPs, NaGdF4:Yb,Tm@NaGdF4) on graphitic-phase carbon nitride (g-C3N4) nanosheets (one photosensitizer). Then, the as-fabricated nanocomposite and carbon dots (another photosensitizer) were assembled in ZIF-8 metal-organic frameworks through an in situ growth process, realizing the dual-photosensitizer hybrid system employed for PDT via stepwise water splitting. In this system, the UCNPs can convert deep-penetration and low-energy near-infrared light to higher-energy ultraviolet-visible emission, which matches well with the absorption range of the photosensitizers for reactive oxygen species (ROS) generation without sacrificing its efficacy under ZIF-8 shell protection. Furthermore, the UV light emitted from UCNPs allows successive activation of g-C3N4 and carbon dots, and the visible light from carbon dots upon UV light excitation once again activate g-C3N4 to produce ROS, which keeps the principle of energy conservation thus achieving maximized use of the light. This dual-PDT system exhibits excellent antitumor efficiency superior to any single modality, verified vividly by in vitro and in vivo assay.

Near-infrared light activated photodynamic therapy of THP-1 macrophages based on core-shell structured upconversion nanoparticles

Upconversion nanoparticles (UCNPs) with fascinating properties hold great potential as nanotransducers for solving the light penetration problem that traditional photodynamic therapy (PDT) is facing. In this report, the synthesis and utility of UCNPs/silica core-shell structured nanoparticles for upconversion (UC) PDT and imaging of THP-1 macrophages were described. The UCNPs (NaYF4:Yb, Er) with a uniform diameter of 28 ± 1 nm were synthesized as core and 10 nm thick biocompatible mesoporous silica was coated as shell. Photosensitizer (PS) was covalently grafted inside mesoporous silica shell. Upon excitation, NIR light is converted into visible one by UCNPs for the absorption of PS to generate singlet oxygen for killing THP-1 macrophages and inhibiting the development of atherosclerosis. The fluorescence images showed the resulting nanoparticles are readily taken up by macrophages and TEM results indicated that they are highly phototoxic. The statistical in vitro results revealed PDT could cause the apoptosis of THP-1 macrophages with a remarkable therapeutic efficacy of cell inhibition ratio of 40%.

Paramagnetism and improved upconversion luminescence properties of NaYF4:Yb,Er/NaGdF4 nanocomposites synthesized by a boiling water seed-mediated route

In a route boiling water served as reaction medium, a stoichiometric amount of rare-earth compound and fluoride are put into this system to form α-NaYF4:Yb, Er nuclei. Then prepared sample is heated at elevated temperature to improve the fluorescence intensity, and next a NaGdF4 shell grows on the surface of NaYF4 nuclei. NaYF4:Yb,Er/NaGdF4 core–shell structured upconversion nanoparticles (CSUCNPs) have been successfully synthesized by above route. The use of boiling water decreases the cubic-to-hexagonal phase transition temperature of NaYF4:Yb,Er to 350°C and increases its upconversion (UC) luminescence intensity. A heterogeneous NaGdF4 epitaxially growing on the surface of Ln3+-doped NaYF4 not only improves UC luminescence, but also creates a paramagnetic shell, which can be used as contrast agents in magnetic resonance imaging (MRI). The solution of CSUCNPs shows bright green UC fluorescence under the excitation at 980 nm in a power density only about 50 mW·cm–2. A broad spectrum with a dominant resonance at g of about 2 is observed by the electron paramagnetic resonance (EPR) spectrum of CSUCNPs. Above properties suggest that the obtained CSUCNPs could be potential candidates for dual-mode optical/magnetic bioapplications.

Mesoporous NaYbF4@NaGdF4 core-shell up-conversion nanoparticles for targeted drug delivery and multimodal imaging

We developed a facile strategy to obtain a new kind of mesoporous core-shell structured up-conversion nanoparticles (mUCNPs), composed of a NaYbF4:2%Er core and a mesoporous NaGdF4 shell. This mesoporous shell not only enhanced the up-conversion luminescence but also endowed many other functionalities of the nanoparticles such as drug delivery and bio-imaging capabilities. Moreover, after being conjugated with polyethylenimine (PEI) and folic acid (FA), core-shell mUCNPs exhibited good water dispersibility, enhanced drug delivery efficiency, and remarkable targeting ability to cancer cells. To certify the folate receptors (FR)-mediated targeted drug delivery, cell viability assay, cell up-conversion luminescence imaging and flow cytometry analysis were carried out. Furthermore, apart from the application for targeted drug delivery, the as-prepared core-shell mUCNPs could also be employed as the contrast agents for X-ray computed tomography (CT) and magnetic resonance (MR) imaging, because of the strong X-ray attenuation ability of Yb and high longitudinal molar relaxivity (r1) of Gd in the nanoparticles, providing the potential for simultaneously bio-imaging and cancer-targeting therapy.

Yolk–Shell Upconversion Nanocomposites for LRET Sensing of Cysteine/Homocysteine

The fabrication of lanthanide upconversion nanocomposites as probes has become a new research hotspot due to its special advantages via utilizing upconversion luminescence (UCL) as a detection signal. Herein, a hybrid organic dye modified upconversion nanophosphor is successfully developed as a nanoprobe for cysteine/homocysteine. Yolk-shell structured upconversion nanoparticles (YSUCNP) with lanthanide upconversion nanophosphor as moveable core and silica as mesoporous shell are synthesized, and a colorimetric chemodosimeter for cysteine/homocysteine is accommodated in the hollow cavities. Thus, cysteine/homocysteine can be quantitatively detected on the basis of luminescent resonance energy transfer (LRET) in a UCL turn-off pattern. The dye-loaded YSUCNP possess good dispersibility in aqueous solution; thus detection of the targeted molecule can be achieved in pure water. Cellular experiments carried out with laser-scanning upconversion luminescence microscopy further demonstrate that the dye-loaded YSUCNP can serve as an intracellular nanoprobe to detect cysteine/homocysteine. Moreover, this dye-loading protocol can be developed as a common approach to construct other chemodosimeter-modified UCNP hybrid nanoprobes, as proved by a UCL turn-on style sensor for cyanide.

利用核壳结构实现纳米颗粒的多色上转换发光

Multicolor fluorescence labeling techniques used in biological multiplex detection can achieve fast,real-time,simultaneous information for a large number of target bio-molecules.Using upconversion nanoparticles as multicolor fluorescent probes can effectively decrease the influence of auto-fluorescence from biological molecules on the fluorescence signal from the nanoparticles.In this paper,the core-shell structured upconversion nanoparticles were prepared by a facile solvothermal method using polyvinylpyrrolidone( PVP) as the surfactant.By co-doping sensitizer and activator ions in the cores and / or shells,the relative intensity of the emission peak was changed.The multicolor fluorescence was obtained from different nanoparticles with different color and intensity of the emission spectra.These nanoparticles were spherical and their sizes were about 30 nm.With the excitation of a 980 nm diode laser,those nanoparticles emitted bright upconversion luminescence from red to blue-violet.

In Vivo Multimodality Imaging and Cancer Therapy by Near-Infrared Light-Triggered trans-Platinum Pro-Drug-Conjugated Upconverison Nanoparticles

Controlling anticancer drug activity and release on demand is very significant in cancer therapy. The photoactivated platinum(IV) pro-drug is stable in the dark and can be activated by UV light. In this study, we develop a multifunctional drug delivery system combining upconversion luminescence/magnetic resonance/computer tomography trimodality imaging and NIR-activated platinum pro-drug delivery. We use the core-shell structured upconversion nanoparticles to convert the absorbed NIR light into UV to activate the trans-platinum(IV) pro-drug, trans,trans,trans-[Pt(N3)2(NH3)(py)(O2CCH2CH2COOH)2]. Compared with using the UV directly, the NIR has a higher tissue penetration depth and is less harmful to health. Meanwhile, the upconversion nanoparticles can effectively deliver the platinum(IV) pro-drugs into the cells by endocytosis. The mice treated with pro-drug-conjugated nanoparticles under near-infrared (NIR) irradiation demonstrated better inhibition of tumor growth than that under direct UV irradiation. This multifunctional nanocomposite could be used as multimodality bioimaging contrast agents and transducers by converting NIR light into UV for control of drug activity in practical cancer therapy.

Graphene oxide covalently grafted upconversion nanoparticles for combined NIR mediated imaging and photothermal/photodynamic cancer therapy

Theranostics, the integration of diagnostics and therapies, has become a new concept in the battles with various major diseases such as cancer. Here, we report a multifunctional nanoplatform, which is developed by covalently grafting core–shell structured upconversion nanoparticles (UCNPs) with nanographene oxide (NGO) via bifunctional polyethylene glycol (PEG), and then loading phthalocyanine (ZnPc) on the surface of NGO. The obtained UCNPs-NGO/ZnPc nanocomposites are not only be used as upconversion luminescence (UCL) imaging probes of cells and whole-body animals with high contrast for diagnosis, but also can generate cytotoxic singlet oxygen under light excitation for photodynamic therapy (PDT), as well as rapidly and efficiently convert the 808 nm laser energy into thermal energy for photothermal therapy (PTT). A remarkably improved and synergistic therapeutic effect compared to PTT or PDT alone is obtained, providing high therapeutic efficiency for cancer treatment. Therefore, benefiting from the unique multifunctional hybrid nanostructure, UCNPs-NGO/ZnPc nanocomposites developed herein are promising as an integrated theranostic probe for potential UCL image-guided combinatorial PDT/PTT of cancer.