Molecularly imprinted polymer based on upconversion nanoparticles for highly selective and sensitive determination of Ochratoxin A

A novel molecularly imprinted polymer (MIP) based on upconversion nanoparticles (UCNPs) was successfully synthesized for determination of Ochratoxin A (OTA). The MIP was developed on the silica-coated UCNPs using N-(1-hydroxy-2-naphthoyl amido)-(L)-phenylalanine (HNA-Phe) as the alternative template. The final composite combined the advantages of the high selectivity of MIP with the high fluorescence intensity of UCNPs which was selective and sensitive to OTA. Under the optimal condition, the fluorescence intensity of UCNPs@SiO2@MIP decreases linearly when the concentration of OTA increases from 0.05 to 1.0 mg/L. The detection limit of OTA with the method was 0.031 mg/L. At three spiked concentration levels (50, 100 and 200 μg/kg), the recovery ranges of OTA in corn, rice and feed are 88.0%–91.6%, 80.2%–91.6% and 89.2%–90.4%, respectively.

Upconversion Nanoparticles-Encoded Hydrogel Microbeads-Based Multiplexed Protein Detection

Fluorescently encoded microbeads are in demand for multiplexed applications in different fields.Compared to organic dye-based commercially available Luminex's x MAP technology, upconversion nanoparticles(UCNPs) are better alternatives due to their large antiStokes shift, photostability, nil background, and single wavelength excitation. Here, we developed a new multiplexed detection system using UCNPs for encoding poly(ethylene glycol) diacrylate(PEGDA) microbeads as well as for labeling reporter antibody. However, to prepare UCNPs-encoded microbeads, currently used swellingbased encapsulation leads to non-uniformity, which is undesirable for fluorescence-based multiplexing. Hence,we utilized droplet microfluidics to obtain encoded microbeads of uniform size, shape, and UCNPs distribution inside. Additionally, PEGDA microbeads lack functionality for probe antibodies conjugation on their surface.Methods to functionalize the surface of PEGDA microbeads(acrylic acid incorporation, polydopamine coating)reported thus far quench the fluorescence of UCNPs. Here,PEGDA microbeads surface was coated with silica followed by carboxyl modification without compromising the fluorescence intensity of UCNPs. In this study, droplet microfluidics-assisted UCNPs-encoded microbeads of uniform shape, size, and fluorescence were prepared.Multiple color codes were generated by mixing UCNPs emitting red and green colors at different ratios prior to encapsulation. UCNPs emitting blue color were used to label the reporter antibody. Probe antibodies were covalently immobilized on red UCNPs-encoded microbeads for specific capture of human serum albumin(HSA) as a model protein. The system was also demonstrated for multiplexed detection of both human C-reactive protein(hCRP) and HSA protein by immobilizing anti-h CRP antibodies on green UCNPs.

TiO_2 composite nanotubes embedded with CdS and upconversion nanoparticles for near infrared light driven photocatalysis

We report a colloidal process to coat a layer of TiO2onto SiO2composite nanofibers containing embedded CdS and upconversion nanoparticles(UCNPs).The SiO2composite nanofibers were fabricated by electrospinning.To improve the energy transfer efficiency,UCNPs and CdS nanoparticles were bound in close proximity to each other within the SiO2matrix.β‐NaYF4:Yb(30%),Tm(0.5%)@NaYF4:Yb(20%),Er(2%)core–shell nanoparticles were used as nanotransducers for near infrared light.These nanoparticles exhibited enhanced upconversion fluorescence compared withβ‐NaYF4:Yb(30%),Tm(0.5%)orβ–NaYF4:Yb(30%),Tm(0.5%)@NaYF4nanoparticles.The morphologies,size and chemical compositions have been extensively investigated using field emission scanning electron microscopy(FESEM),transmission electron microscopy(TEM),X‐ray diffraction(XRD)and X‐ray photoelectron spectra(XPS),respectively.The TEM images showed that the TiO2composite nanotubes were embedded with a large amount of UCNPs and CdS nanoparticles.The composite TiO2nanotubes degraded more than90%of rhodamine B(RhB)dye during20min of irradiation by simulated solar light.In particular,more than50%of RhB was decomposed in70min,under irradiation of near infrared light(NIR).This high degradation was attributed to the full spectrum absorption of solar light,and the enhanced transfer efficiency for near infrared light.The as‐prepared nanostructures can harness solar energy,and provide an alternative to overcome energy shortages and environmental protection.

Ultra-stable near-infrared Tm^(3+)-doped upconversion nanoparticles for in vivo wide-field two-photon angiography with a low excitation intensity

Two-photon luminescence with near-infrared(NIR)excitation of upconversion nanoparticles(NPs)is of great importance in biological imaging due to deep penetration in high-scattering tissues,low auto-luminescence and good sectioning ability.Unfortunately,common two-photon luminescence is in visible band with an extremely high exciation power density,which limits its application.Here,we synthesized NaYF_(4):Yb/Tm@NaYF_(4)upconversion NPs with strong twophoton NIR emission and a low excitation power density.Furthermore,NaYF_(4):Yb/Tm@NaYF_(4)@SiO_(2)@OTMS@F127 NPs with high chemical stability were obtained by a modified multilayer coating method which was applied to upconversion NPs for thefirst time.In addition,it is shown that the as-prepared hydrophillic upconversion NPs have great biocompatibility and kept stable for 6 hours during in vivo whole-body imaging.The vessels with two-photon luminescence were clear even under an excitation power density as low as 25mW/cm^(2).Vivid visualizations of capillaries and vessels in a mouse brain were also obtained with low background and high contrast.Because of cheaper instruments and safer power density,the NIR two-photon luminescence of NaYF_(4):Yb/Tm@NaYF_(4)upconversion NPs could promote wider application of two-photon technology.The modified multilayer coating method could be widely used for upconversion NPs to increase the stable time of the in vivo circulation.Our work possesses a great potential for deep imaging and imaging-guided treatment in the future.

Unveiling the origin of performance enhancement of photovoltaic devices by upconversion nanoparticles

To better utilize the infrared(IR)region in sunlight for photovoltaic devices(PVs),upconversion nanoparticles(UCNPs)have been proposed to improve power conversion efficiency(PCE).However,researchers recently have found that the upconversion(UC)effect is negligible in PVs performance improvement for their ultra-low UC photoluminescence quantum yields of UCNPs solid film,while the real mechanism of UCNPs in PVs has not been clearly studied.Herein,based on the material inorganic perovskitesγ-CsPbI_(3),NaYF_(4):20%Yb^(3+),2%Er^(3+)UCNPs were integrated into different transport layer to optimize device performance.Compared with reference device,the short-circuit current density and PCE of optimized device reached 20.87 mA/cm^(2)(20.39 mA/cm^(2))and 18.34%(17.72%),respectively,without sacrificing open-circuit voltage and filling factor.Further experimental characterizations verified that the improved performance was attributable to enhanced visible light absorption instead of IR.To theoretically explain the statement,the light field distribution in device was simulated and the absorption in different layers was calculated.The results revealed that the introduction of UCNPs with different refractive index from other layers caused light field disturbance,and improved visible light captured by γ-CsPbI_(3).Importantly,through experiments and theoretical calculation,the research deeply explored the potential mechanism of UCNPs in optimizing PVs performance.

Characterizing the luminescent properties of upconversion nanoparticles in single and densely packed state

Luminescent properties of Er^(3+)-and Yb^(3+)-co-doped CaF_(2)upconversion nanoparticles(UCNPs)were investigated in single particle and densely-packed states with a custom-built microscope.The single UCNPs exhibit linear dependency of luminescent intensity on excitation power while the densely-packed UCNPs exhibit a 2-order power law-dependency indicating a two-photon absorption process.Time-domain luminescence intensity measurements were performed and the curves were fitted to excitationnemission rate functions based on a simplified three-state model.The results indicate that the intermediates in single particles are much less and saturated in a short time,and there are strong couplings of the ground states and intermediate states between neighboring UCNPs in densely packed UCNPs.

Engineering CeO_(2)/CuO heterostructure anchored on upconversion nanoparticles with boosting ROS generation-primed apoptosisferroptosis for cancer dynamic therapy

Highly toxic reactive oxygen species(ROS)induced apoptosis and ferroptosis have been considered as significant cell death pathways for cancer therapy.However,insufficient amount of intracellular ROS extremely restricts the therapeutic effect.Toward this,we report a rationally designed nanocomposite(mUCC)with enhanced ROS generation ability,inducing the combination of apoptosis and ferroptosis through synergistic photodynamic therapy(PDT)and chemodynamic therapy(CDT).Under 808 nm near-infrared(NIR)light irradiation,photocatalytic reaction is triggered starting from the separation of electron-hole pairs on the surface of heterojunction(CeO_(2)/CuO),realizing improved ROS production.Simultaneously,mUCC served as Fenton-like agent exhibits considerable ability to generate highly toxic·OH under tumor microenvironment(TME).The boosted accumulation of ROS disrupts the redox balance within tumor cells and results in the integration of apoptosis and ferroptosis.In addition,mUCC shows satisfactory tumor targeting property benefiting from the cancer cell membrane functionalization under the guidance of magnetic resonance imaging(MRI)and NIR fluorescence imaging.The intelligent mUCC with good biocompatibility and excellent antitumor response achieves efficient tumor elimination under synergistic PDT and CDT.This work offers an elective approach for further development of ROS-based therapeutic nanoplatform in cancer therapy.

Dual excitable upconversion nanoparticle@polydopamine nanocomposite with intense red emission and efficient photothermal generation

Integration of strong upconversion emission with deep tissue penetration and stable photothermal generation is of great significance for imaging-guided photothermal therapy under infrared excitation.Herein,the NaYF_(4):Yb^(3+),Ho^(3+),Ce^(3+)@NaGdF_(4):Yb^(3+),Nd^(3+)@NaGdF_(4)core-shell-shell upconversion nanoparticles(UCNPs) with increasing Ce^(3+)doping concentration were firstly synthesized,in which the size manipulation,enhanced red to green emission intensity ratio(IR/IG),980 and 808 nm dual-modal excitations,as well as improved total upco nversion emission intensity can be achieved.After the coating of polydopamine(PDA) through dopamine spontaneous polymerization on the UCNPs surface under alkaline condition,the obtained UCNP@PDA nanocomposites show efficient photothermal effect under 808 nm excitation,while the thickness variation of PDA can be indicated by the upconversion spectra under 980 nm excitation.Interestingly,the photothermal effect of the UCNP@PDA nanocomposites with high IR/IGratio is mo re stable with PDA thickness variation,which bene fits from the structure design that allows PDA to simultaneously absorb the visible emission from inside UCNPs and the external 808 nm infrared light.Further in vitro cytotoxicity assay and photothermal therapy demonstrate that the UCNP@PDA nanocomposite has good biocompatibility and ability to kill tumor cells by photothermal effect under 808 nm excitation.This research may provide a nanoplatform for integrating deep bioimaging with highly stable photothermal therapy without the sacrifice of radiative transitions of rare earth ions.

Modulator-directed assembly of hybrid composites based on metalorganic frameworks and upconversion nanoparticles

Hybrid composites made of metal-organic frameworks(MOFs)and lanthanide-doped upconversion nanoparticles(UCNPs)have attracted considerable interest for their synergistically enhanced functions in various applications such as chemical sensing,photocatalysis,anticounterfeiting and nanomedicine.However,precise assembly of MOF/UCNP hybrid composites with tunable morphologies remains a challenge due to the lack of effective synthetic methods and fundamental understanding of the growth mechanisms.Herein,we propose a modulator-directed assembly strategy to synthesize a series of ZIF-8@UCNP composites(ZIF-8=zeolitic imidazolate framework-8).The UCNPs densely paved on the surface of ZIF-8 microcrystals and endowed the composites with intense upconversion blue emission,which were verified by steady-state/transient photoluminescence(PL)spectroscopy and single-particle imaging.Ethylenediamine(EDA)was firstly used as a modulator to fine-tune the predominant MOF facets and realized distinct morphologies of the composites.By adjusting the concentration of EDA from 0 to 25 mmol/L,the morphology of the ZIF-8@UCNP composites was tuned from rhombic dodecahedron(RD)to truncated rhombic dodecahedron(TRD),cube with truncated edges(CTE),cube,and finally a unique form of interpenetration twins(IT).The nucleation and growth process of the ZIF-8@UCNP composites was monitored by time-dependent scanning electron microscopy(SEM)images and the formation mechanism was thoroughly revealed.Furthermore,we demonstrated that the strategy for assembly of morphology-controllable ZIF-8@UCNP composites was generally applicable to various UCNPs with different sizes and shapes.The proposed strategy is expected to open up new avenues for the controllable synthesis of MOF/UCNP composites toward diverse applications.

Review on the application of upconversion nanomaterials in heavy metal detection

As a widespread element,heavy metals have a significant impact on human health and threaten human health.It is of great significance to develop analytical technologies that can detect heavy metal ions quickly and accurately.In comparison to conventional fluorescent materials such as organic dyes,quantum dot(QD)labels,and carbon quantum dots(CD),fluorescence detection technology utilizing lanthanide(Ln)ion-doped upconversion nanoparticles(UCNPs)stands out due to its distinctive attributes.These include a notably reduced autofluorescence background,enhanced tissue penetration capabilities,biocompatibility with cellular tissues,and minimal photodamage inflicted on biological samples.The utilization of this technology has garnered considerable attention across multiple fields.In the domain of heavy metal detection,traditional laboratory methods necessitate costly instrumentation and a fully equipped laboratory,involving intricate sample processing procedures and protracted detection periods,as well as a demand for skilled personnel.In contrast,the implementation of this material offers rapid and cost-effective detection,significantly mitigating the technical barriers for operators.Consequently,this represents an exceptional avenue to curtail expenses and broaden the scope of detection within the analytical process.This paper reviews the research progress of UCNPs in the detection of heavy metal ions,encompassing a brief elucidation of the luminescence principle of upconversion nanomaterials and commonly used detection principles.Additionally,it provides a detailed overview of the research status of several common non-metal ions and essential heavy metals.Furthermore,it summarizes the current focal points in UCNP detection and discusses the challenges and prospects associated with it.

Highly-Sensitive Multiplexed in vivo Imaging Using PEGylated Upconversion Nanoparticles

Lanthanide-based upconversion nanoparticles(UCNPs)have been widely explored in various fields,including optical imaging,in recent years.Although earlier work has shown that UCNPs with different lanthanide(Ln3+)dopants exhibit various colors,multicolor-especially in vivo multiplexed biomedical imaging-using UCNPs has rarely been reported.In this work,we synthesize a series of UCNPs with different emission colors and functionalize them with an amphiphilic polymer to confer water solubility.Multicolor in vivo upconversion luminescence(UCL)imaging is demonstrated by imaging subcutaneously injected UCNPs and applied in multiplexed in vivo lymph node mapping.We also use UCNPs for multicolor cancer cell labeling and realize in vivo cell tracking by UCL imaging.Moreover,for the first time we compare the in vivo imaging sensitivity of quantum dot(QD)-based fluorescence imaging and UCNP-based UCL imaging side by side,and find the in vivo detection limit of UCNPs to be at least one order of magnitude lower than that of QDs in our current non-optimized imaging system.Our data suggest that,by virtue of their unique optical properties,UCNPs have great potential for use in highly-sensitive multiplexed biomedical imaging.

Upconversion nanoparticles:Recent strategies and mechanism based applications

Upconversion nanoparticles(UCNPs)doped with lanthanides can convert near-infrared excitation into UV and visible emissions.Because of their relatively high emission efficiency,UCNPs are appealing materials for use in a variety of sectors.UCNPs are known for low auto-fluorescence,excellent chemical and thermal photo-stability,deep tissue penetration,exceptional biocompatibility,low toxicity,color purity,and ease of surface functionalization.In this review,we explain a few recent strategies to boost the efficiency and luminescence of upconversion nanoparticles and minimize quenching by fabricating them as core/shell,nanofibers,or heavily doped lanthanides.Applications of UCNPs in drug delivery,Photodynamic therapy(PDT),biosensors,bioimaging,and optogenetics are also discussed along with their mechanism of action.Our motivation for this review is to understand the working mechanism of UCNPs and their applications in various fields.

Improving acceptor efficacy rather than energy transfer efficiency:Dominant contribution of monomers of acceptors modified on upconversion nanoparticles

Upconversion nanosensitizers have been widely considered to have important applications in the treatment of major diseases such as tumors and the utilization of solar energy.Majority of the efforts so far have been focused on improving the efficiency of energy transfer(ET)between upconversion nanoparticles(UCNPs)and the anchored sensitizers with premise that high ET efficiency will lead to high acceptor efficacy.This premise is,however,proved by our current work to be invalid for commonly used load.Interaction between adjacent sensitizing molecules was found to be critical which undermines the amount of excited monomer sensitizers and thus fades the efficacy.Here NaYF_(4):Yb^(3+),Er^(3+)UCNPs and rose bengal(RB)photosensitizer molecules were used as the model energy donors and acceptors,respectively.Contrary to monotonous increase of the ET efficiency from UCNPs to RB species with increasing RB loading,acceptor efficacy characterized by the reactive oxygen species,as well as the RB fluorescence,exhibits bizarre dependence on the RB loading.The underlying mechanism was well studied by the steady-state and time-resolved spectroscopy of a series of samples.RB aggregates are believed to be responsible for the severe deviation between the ET efficiency and acceptor efficacy.The conclusion was validated by in vitro test where the photodynamic therapy with the most monomer RB in UCNPs-RB nanosensitizers kills 35.8%more cells than that with the highest RB loading.This understanding sheds light on construction of new ET based nanosystems for broad applications,such as medicine,solar energy utilization and optical storage.

Core-satellite metal-organic framework@upconversion nanoparticle superstructures via electrostatic self-assembly for efficient photodynamic theranostics

The nanoplatforms based on upconversion nanoparticles(UCNPs)have shown great promise in amplified photodynamic therapy(PDT)triggered by near-infrared(NIR)light.However,their practical in vivo applications are hindered by the overheating effect of 980 nm excitation and low utilization of upconversion luminescence(UCL)by photosensitizers.To solve these defects,core-satellite metal-organic framework@UCNP superstructures,composed of a single metal-organic framework(MOF)NP as the core and Nd3+-sensitized UCNPs as the satellites,are designed and synthesized via a facile electrostatic self-assembly strategy.The superstructures realize a high co-loading capacity of chlorin e6(Ce6)and rose bengal(RB)benefitted from the highly porous nature of MOF NPs,showing a strong spectral overlap between maximum absorption of photosensitizers and emission of UCNPs.The in vitro and in vivo experiments demonstrate that the dual-photosensitizer superstructures have trimodal(magnetic resonance(MR)/UCL/fluorescence(FL))imaging functions and excellent antitumor effectiveness of PDT at 808 nm NIR light excitation,avoiding the laser irradiation-induced overheating issue.This study provides new insights for the development of highly efficient PDT nanodrugs toward precision theranostics.

Upconversion nanoparticles regulated drug&gas dual-effective nanoplatform for the targeting cooperated therapy of thrombus and anticoagulation

Thromboembolism is the leading cause of cardiovascular mortality.Currently,for the lack of targeting,short half-life,low bioavailability and high bleeding risk of the classical thrombolytic drugs,pharmacological thrombolysis is usually a slow process based on micro-pumping.In addition,frequently monitoring and regulating coagulation functions are also required during(and after)the process of thrombolysis.To address these issues,a targeted thrombolytic and anticoagulation nanoplatform(UCATS-UK)is developed based on upconversion nanoparticles(UCNPs)that can convert 808 or 980 nm near-infrared(NIR)light into UV/blue light.This nanoplatform can target and enrich in the thrombus site.Synergistic thrombolysis and anticoagulation therapy thus could be realized through the controlled release of urokinase(UK)and nitric oxide(NO).Both in vitro and in vivo experiments have confirmed the excellent thrombolytic and anticoagulative capabilities of this multifunctional nanoplatform.Combined with the unique fluorescent imaging capability of UCNPs,this work is expected to contribute to the development of clinical thrombolysis therapy towards an integrated system of imaging,diagnosis and treatment.

Upconversion nanoparticles@AgBiS_(2) core-shell nanoparticles with cancer-cell-specific cytotoxicity for combined photothermal and photodynamic therapy of cancers

UCNPs@AgBiS_(2) core-shell nanoparticles that AgBiS_(2) coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of AgBiS_(2) can be improved from 14.7% to 45% due to the cross relaxation between Nd ions and AgBiS_(2). The doping concentration of Nd ions played a critical role in the production of reactive oxygen species (ROS) and enhanced the photothermal conversion efficiency. The NaYF4:Yb/Er/Nd@NaYF4:Nd nanoparticles endows strong upcon-version emissions when the doped concentration of Nd ions is 1% in the inner core, which excites the AgBiS_(2) shell to produce ROS for photodynamic therapy (PDT) of cancer cells. As a result, the as-prepared NaYF4:Yb/Er/ Nd@NaYF4:Nd@AgBiS_(2) core-shell nanoparticles showed combined photothermal/photodynamic therapy (PTT/ PDT) against malignant tumors. This work provides an alternative near-infrared light-active multimodal nano-structures for applications such as fighting against cancers.

Sustainable and invisible anti-counterfeiting inks based on waterborne polyurethane and upconversion nanoparticles for leather products

Counterfeit leather products infringe the intellectual property rights of the business,cause enormous economic loss,and negatively influence the business enthusiasm for innovation.However,traditional anti-counterfeiting materials for leather products suffer from complicated fabrication procedures,photobleaching,and high volatile organic com-pound(VOC)emissions.Here,a sustainable and invisible anti-counterfeiting ink composed of waterborne polyure-thane and water-dispersible lanthanide-doped upconversion nanoparticles(UCNPs)featuring ease of preparation,high photostability,non-toxicity,low VOC emissions,and strong adhesion strength for leather products is designed and synthesized.After decorating on the surface of leather products,the obtained patterns are invisible under normal light conditions.Upon irradiation at 808 nm,the invisible patterns can be observed by naked eyes due to the visible light emitted by 808 nm excited UCNPs.Our approach described here opens a new pathway to realize the long-term,stable anti-counterfeiting function of leather products.

Dissection the endocytic routes of viral capsid proteins-coated upconversion nanoparticles by single-particle tracking

Real-time exploring the cellular endocytic pathway of viral capsid proteins(VCPs)functionalized nanocargos at the single-particle level can provide deep insight into the kinetic information involved in virus infection.In this work,porcine circovirus type 2(PCV2)VCPs with different functions are modified onto the surface of upconversion nanoparticles(VCPs-UCNPs)to investigate the cellular internalization process in real-time.Clathrin-mediated endocytosis is found to be the essential uptake mechanism for these VCPs-UCNPs.Besides,it is verified that P_(1)-UCNPs(PCV2 VCPs with nuclear localization signal,namely P1)can be easily assembled close to the perinuclear area,which is different from that of P_(2)-UCNPs(PCV2 VCPs without nuclear localization signal,namely P_(2)).Interestingly,multistep entry processes are observed.Particularly,confined diffusion is observed during the transmembrane process.The intracellular transport of VCPs-UCNPs is dependent on microtubules toward the cell interior.During this process,P_(1)-UCNPs display increased velocities with active transport,while diffusion much faster around the perinuclear area.But for P_(2)-UCNPs,there are only two phases involved in their endocytosis process.This study presents distinct dynamic mechanisms for the nanocargos with different functions,which would make a useful contribution to the development of robust drug delivery systems.

A DNA sensor based on upconversion nanoparticles and two-dimensional dichalcogenide materials

We demonstrate the fabrication of a new DNA sensor that is based on the optical interactions occurring between oligonucleotide-coated NaYF4:Yb^(3+);Er^(3+) upconversion nanoparticles and the two-dimensional dichalcogenide materials,MoS_(2) and WS_(2).Monodisperse upconversion nanoparticles were functionalized with single-stranded DNA endowing the nanoparticles with the ability to interact with the surface of the two-dimensional materials via van der Waals interactions leading to subsequent quenching of the upconversion fluorescence.By contrast,in the presence of a complementary oligonucleotide target and the formation of double-stranded DNA,the upconversion nanoparticles could not interact with MoS_(2) and WS_(2),thus retaining their inherent fluorescence properties.Utilizing this sensor we were able to detect target oligonucleotides with high sensitivity and specificity whilst reaching a concentration detection limit as low as 5 mol·L^(-1),within minutes.

Continuous synthesis of ultrasmall core-shell upconversion nanoparticles via a flow chemistry method

A continuous synthesis method for the less than 10 nm core-shell upconversion nanoparticles was developed via coiled tube embedded flask reactors and a flow solvothermal co-participation reaction up to 300℃.Fast nucleation of hexagonal nanocrystals in less than 9 min residence time was achieved owing to the excellent heating ability of the reactors,and a two-step reaction strategy was created for the synthesis of β-NaYF4:Gd,Yb,Er/Ho/Tm@NaYF_(4) particles without intermediate purification.