An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(C...An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.展开更多
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 ...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.展开更多
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) ar...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.展开更多
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...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.展开更多
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 impro...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.展开更多
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...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.展开更多
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 goo...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.展开更多
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 foun...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.展开更多
Surface modification of different functional molecules onto NaREF_(4)(RE=rare earth)upconversion nanoparticles(UCNPs)impart their multiple functionalities.Functional molecules can be loaded onto NaREF_(4) UCNPs throug...Surface modification of different functional molecules onto NaREF_(4)(RE=rare earth)upconversion nanoparticles(UCNPs)impart their multiple functionalities.Functional molecules can be loaded onto NaREF_(4) UCNPs through the formation of coordination bonds between the surface-exposed RE^(3+) ions and the appropriate chemical groups of functional molecules.The density of surface RE^(3+) ions directly determines the loading efficiency of Na REF4 UCNPs.However,NaREF_(4) is a binary cation system,rendering the surface-distributed Na;and RE^(3+) ions remains a mystery.Here,we develop an effective strategy to significantly enhance the density of surface RE^(3+) ions,thus maximizing the loading capacity of NaREF_(4) UCNPs.This strategy is based on a heterovalent cation exchange(HCE)reaction in the surface region in which Na^(+)ions are replaced by RE^(3+) ions.The density of surface ligands enhances from 3.6 to 8.8 molecules/nm^(2) after reaction,suggesting that the loading efficiency increases by approximately 150%.Benefiting from the improved loading capacity,we demonstrate such surface-RE-rich nanoparticles have the ability to offer higher colloidal stability and more desirable photodynamic therapy(PDT)efficacy.This work not only advances our understanding of cation exchange reactions in RE-based nanoparticles,but also provides significant value for considerable applications such as sensing,bioimaging,and therapy.展开更多
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 lin...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.展开更多
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 fo...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.展开更多
Antibacterial upconversion nanoparticles(UCNP)-based photodynamic-chemical combined therapy(UCNP-aPCCT)provides an ideal method to solve the problem of antibiotic-resistant bacteria in deep-tissue infections.Saponin i...Antibacterial upconversion nanoparticles(UCNP)-based photodynamic-chemical combined therapy(UCNP-aPCCT)provides an ideal method to solve the problem of antibiotic-resistant bacteria in deep-tissue infections.Saponin is a kind of natural product exhibiting promising antibacterial activity.Curcumin is also a natural product that could be used as photosensitizer for antibacterial photodynamic therapy(aPDT).展开更多
Information security has attracted broad attention in today’s information age,and information encryption on paper has been widely studied since paper is still the most important information carrier.Fluorescent inks a...Information security has attracted broad attention in today’s information age,and information encryption on paper has been widely studied since paper is still the most important information carrier.Fluorescent inks are commonly used in information encryption on paper,but they suffer from background fluorescence interference.Herein,we develop a background-free and easy-to-perform method for information encryption based on the inkjet printing of upconversion nanoparticles(UCNPs).The UCNPs can efficiently eliminate background fluorescence interference since phosphors in paper cannot be activated by near-infrared(NIR)light.Moreover,owing to their small size,excellent dispersibility and good stability,UCNP inks can be directly applied to commercial inkjet printers for convenient and high-throughput information encryption on paper.Information was easily printed on different kinds of paper substrates and the information can only be visualized under NIR light excitation.Furthermore,a novel information encryption strategy was designed by utilizing UCNPs with different excitation wavelengths.Only excitation at the defined wavelength can obtain the correct information.This proposed information encryption strategy can completely avoid background fluorescence interference,and it also features easy operation,high throughput as well as low costs,indicating its good promise to serve as a household encryption method in our daily life.展开更多
The applications of upconversion nanoparticles in biodetection,bioimaging,and lighting have greatly fuelled a growing demand for enhancing their brightness.The brightness of upconversion nanoparticles is fundamentally...The applications of upconversion nanoparticles in biodetection,bioimaging,and lighting have greatly fuelled a growing demand for enhancing their brightness.The brightness of upconversion nanoparticles is fundamentally limited by the low doping concentration of either activator or sensitizer ions,in spite of the progress of rational controlling nanoparticles to improve performance.Although NaYbF_(4)nano-particles possessing the largest amount of sensitizers(Yb^(3+))have been proposed as a promising alterna-tive host to achieve bright upconversion luminescence,systemic explorations in synthesizing NaYbF_(4)nanoparticles have scarcely been performed.In this work,we report the systematic synthesis and fine control of monodisperse NaYbF_(4)nanoparticles through a canonical high-temperature co-precipitation method.The phase and morphology of NaYbF_(4)nanoparticles can be rationally tuned,through modulat-ing the amount of NH4 F,amount of NaOH,temperature,and time,respectively.The heating rate has also been found to exert an effect on the phase and morphology evolution of NaYbF_(4)nanoparticles for the first time.The size of NaYbF_(4)nanoparticles can be modulated from hundreds to several nanometers,in addition to the variation of their phase and morphology.The optical properties of NaYbF_(4):Er upconver-sion nanoparticles obtained under different reaction parameters have been investigated,and moreover,their potential applications in imaging deep tissue and photodynamic therapy have been explored.Unravelling the phase and morphology evolution of NaYbF_(4)nanoparticles is expected to hold great potential for boosting the brightness of upconversion nanoparticles.展开更多
Lanthanide-doped upconversion nanoparticles are undergoing extensive investigations in many fields,particularly in biophotonics and photophysics.In an attempt to boost upconversion emission intensities,Yb-based fluori...Lanthanide-doped upconversion nanoparticles are undergoing extensive investigations in many fields,particularly in biophotonics and photophysics.In an attempt to boost upconversion emission intensities,Yb-based fluoride crystals have been recently identified as more efficient alternatives to classical NaYF_(4) crystals.Yb-Based fluoride crystals featuring a maximal occupancy of the host lattice by Yb^(3+)sensitizers facilitate the utilization of excitation light and promote energy transfer to upconverting activators,which contributes to a significant enhancement of upconversion luminescence.In this article,we present a survey of recent studies on chemical preparations of Yb-based fluoride nanoparticles with well-defined size and morphology.We show that these Yb-based upconversion nanoparticles are playing important roles in a few emerging applications such as optogenetics,biodetection and upconversion lasing.展开更多
The generation of reactive oxygen species(ROS)is often limited by the overexpression of glutathione(GSH)in the tumor microenvironment(TME)and the penetration depth of visible light.In view of this,we designed biodegra...The generation of reactive oxygen species(ROS)is often limited by the overexpression of glutathione(GSH)in the tumor microenvironment(TME)and the penetration depth of visible light.In view of this,we designed biodegradable Cu/ZIF-8 shell-coated lanthanide-doped nanoparticles and loaded with a photosensitizer(Rose Bengal),and fabricated a NIR-triggered nanocomposite NaYF_(4):20%Yb,2%Er@Cu/ZIF-8/RB@F127(UCZRF)for the synergistic treatment of CDT and PDT.Interestingly,the UCZRF nanostructures can specifically release RB and Cu^(2+)in the acidic tumor microenvironment(TME).Cu^(2+)depletes GSH to effectively change the amount of ROS produced by RB under 980 nm laser irradiation,and Cu+from the reduction reaction of GSH reacts with excess hydrogen peroxide(H_(2)O_(2))in the TME to generate hydroxyl radicals(·OH)with high oxidation activity.In such a simple nanosystem,we enhance the anti-tumor effect of CDT and PDT by improving the efficiency of ROS generation.展开更多
Light-based additive manufacturing holds great potential in the field of bioprinting due to its exceptional spatial resolution,enabling the reconstruction of intricate tissue structures.However,printing through biolog...Light-based additive manufacturing holds great potential in the field of bioprinting due to its exceptional spatial resolution,enabling the reconstruction of intricate tissue structures.However,printing through biological tissues is severely limited due to the strong optical scattering within the tissues.The propagation of light is scrambled to form random speckle patterns,making it impossible to print features at the diffraction-limited size with conventional printing approaches.The poor tissue penetration depth of ultra-violet or blue light,which is commonly used to trigger photopolymerization,further limits the fabrication of high cell-density tissue constructs.Recently,several strategies based on wavefront shaping have been developed to manipulate the light and refocus it inside scattering media to a diffraction-limited spot.In this study,we present a high-resolution additive manufacturing technique using upconversion nanoparticles and a wavefront shaping method that does not require measurement from an invasive detector,i.e.,it is a non-invasive technique.Upconversion nanoparticles convert near-infrared light to ultraviolet and visible light.The ultraviolet light serves as a light source for photopolymerization and the visible light as a guide star for digital light shaping.The incident light pattern is manipulated using the feedback information of the guide star to focus light through the tissue.In this way,we experimentally demonstrate that near-infrared light can be non-invasively focused through a strongly scattering medium.By exploiting the optical memory effect,we further demonstrate micro-meter resolution additive manufacturing through highly scattering media such as a 300-μm-thick chicken breast.This study provides a concept of high-resolution additive manufacturing through turbid media with potential application in tissue engineering.展开更多
A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK...A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK-CUR-TPP)to enable synergistic tumor therapy via photodynamic(PDT),chemodynamic(CDT),and mild photothermal therapy(mPTT).In this strategy,AuNPs attached to the surface serve as a“pore locker”,cloaking CeO_(2)and CUR before entering tumor cells.UCNPs convert near-infrared(NIR)light into UV and visible light emission,simultaneously initiating AuNP aggregation via photoclick chemistry,CeO_(2)-mediated reactive oxygen species(ROS)generation,and TPP-CUR-driven PDT.The CeO_(2)amplifies oxidative stress by depleting glutathione(GSH)and catalyzing ROS production(O_(2)^(·-)and·OH),while releasing oxygen to relieve tumor hypoxia.The release of TPP-CUR not merely resumes the negativity of the surface,but also disrupts mitochondrial function and downregulates heat shock proteins(HSPs),further sensitizing tumor cells to mPTT(~45℃)performed by light-induced AuNP aggregation after detachment due to electrostatic repulsion.Importantly,ROS-scavenging ability post-PTT of CeO_(2)has been demonstrated to effectively mitigate excessive inflammation and prevent severe scab formation.This fully integrated,lightand ROS-responsive nanoplatform affords significant therapeutic efficacy in 4T1 tumor-bearing BALB/c mice,reducing tumor volume from 185 to 27 mm^(3)following a single tail-vein injection.展开更多
Optically responsive composite materials hold significant promise for in vivo diagnostics and targeted therapies.Rare-earthdoped upconversion nanoparticles(UCNPs),renowned for their unique luminescence properties,larg...Optically responsive composite materials hold significant promise for in vivo diagnostics and targeted therapies.Rare-earthdoped upconversion nanoparticles(UCNPs),renowned for their unique luminescence properties,large anti-Stokes shift,excellent biocompatibility,and deep tissue penetration,have emerged as highly promising candidates for advanced phototherapy in biological systems.This review first explores the fundamental mechanisms of upconversion luminescence,as well as synthesis,surface modification,and design strategies to brighten upconversion.It then highlights recent advances and key applications of UCNPs in biological therapy,including upconversion-mediated phototherapy,multimodal therapeutic approaches,and image-guided therapy and surgery.Finally,it discusses the current challenges and opportunities in both fundamental research and clinical translation,providing theoretical insights and practical guidance to support the broader application of UCNPs in biological therapy and clinical medicine.展开更多
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...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.展开更多
文摘An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.
基金SVKM's NMIMS University(PhD/20.08.2020)for providing fellowship to carry out research。
文摘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.
基金the funding support from the Singapore Ministry of Education Academic Research Fund (AcRF Tier 3 Grant MOE2016-T3-1-004, R-397-000274-112 AcRF Tier 1 Grant R-397-000-270-114)
文摘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.
基金Project(17ZYPTJC00050)supported by Science and Technology Committee of Tianjin,ChinaProject(2017YFC1600803)supported by the Ministry of Science and Technology of China
文摘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.
基金supported in part by the National Natural Science Foundation of China(21471043,21304028,51403195,31501576)~~
文摘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.
基金financial support from the National Natural Science Foundation of China(Nos.22174079,21974073).
文摘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.
基金This work is partially supported by National Key Research and Development Program of China(Grant No.2018YFC1407503)the Fundamental Research Funds for the Central Universities(2018FZA5001)The National Natural Science Foundation of China(Grant No.11621101).
文摘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.
基金funded by the National Natural Science Foundation of China(52073131,51902148,61874166,51802024,11974069 and U1832149)the Fundamental Research Funds for the Central Universities(lzujbky-2020-61,lzujbky-2020-64,lzujbky-2021-it31,lzujbky-2021-ct15 and lzujbky-2021-ct01)+2 种基金the Natural Science Foundation of Gansu Province(20JR5RA278 and 20JR5RA24)the LiaoNing Revitalization Talents Program(XLYC1902113)the Science and Technology Program of Qinghai Province(2020-HZ-809)。
文摘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.
基金financially supported by the National Natural Science Foundation of China(Nos.61805083,31801968,and 51802281)。
文摘Surface modification of different functional molecules onto NaREF_(4)(RE=rare earth)upconversion nanoparticles(UCNPs)impart their multiple functionalities.Functional molecules can be loaded onto NaREF_(4) UCNPs through the formation of coordination bonds between the surface-exposed RE^(3+) ions and the appropriate chemical groups of functional molecules.The density of surface RE^(3+) ions directly determines the loading efficiency of Na REF4 UCNPs.However,NaREF_(4) is a binary cation system,rendering the surface-distributed Na;and RE^(3+) ions remains a mystery.Here,we develop an effective strategy to significantly enhance the density of surface RE^(3+) ions,thus maximizing the loading capacity of NaREF_(4) UCNPs.This strategy is based on a heterovalent cation exchange(HCE)reaction in the surface region in which Na^(+)ions are replaced by RE^(3+) ions.The density of surface ligands enhances from 3.6 to 8.8 molecules/nm^(2) after reaction,suggesting that the loading efficiency increases by approximately 150%.Benefiting from the improved loading capacity,we demonstrate such surface-RE-rich nanoparticles have the ability to offer higher colloidal stability and more desirable photodynamic therapy(PDT)efficacy.This work not only advances our understanding of cation exchange reactions in RE-based nanoparticles,but also provides significant value for considerable applications such as sensing,bioimaging,and therapy.
基金The work was supported by the National Key Research and Development Program of China(YFC20170110100)the National Natural Science Foundation of China(NSFC)(Grant Nos.61475185 and 11504409)Natural Science Foundation of Tianjin City(TJNSF)(Grant No.16JCYBJC43800).Xiaohu Chen and Zhengyu Gui contributed equality to this work.
文摘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.
基金Project supported by the National Natural Science Foundation of China(51972052,11604043,11604044,51772122,11674316)Scientific and Technological Developing Scheme of Jilin Province(20190201243JC)+5 种基金Science and Technology Research Project of Education Department of Jilin Province(JJKH20211275KJ)the Fundamental Research Funds for the Central Universities(2412019FZ033)the 111 Project(B13013)Netherlands Organization for Scientific Research in the framework of the Fund New Chemical Innovation(731.015.206)EU H2020-MSCA-ITN-ETN Action program,ISPIC(675743)EU H2020-MSCA-RISE Action program,CANCER(777682)。
文摘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.
基金support from the National Key R&D Program of China(No.2019YFD1002300)the Key R&D Program of Hunan Province(No.2019NK2091)the Guangdong Natural Science Foundation Projects(No.2018B030315010).
文摘Antibacterial upconversion nanoparticles(UCNP)-based photodynamic-chemical combined therapy(UCNP-aPCCT)provides an ideal method to solve the problem of antibiotic-resistant bacteria in deep-tissue infections.Saponin is a kind of natural product exhibiting promising antibacterial activity.Curcumin is also a natural product that could be used as photosensitizer for antibacterial photodynamic therapy(aPDT).
基金supported by the National Natural Science Foundation of China(21422105,21675120)the Ten Thousand Talents Program for Young Talents.
文摘Information security has attracted broad attention in today’s information age,and information encryption on paper has been widely studied since paper is still the most important information carrier.Fluorescent inks are commonly used in information encryption on paper,but they suffer from background fluorescence interference.Herein,we develop a background-free and easy-to-perform method for information encryption based on the inkjet printing of upconversion nanoparticles(UCNPs).The UCNPs can efficiently eliminate background fluorescence interference since phosphors in paper cannot be activated by near-infrared(NIR)light.Moreover,owing to their small size,excellent dispersibility and good stability,UCNP inks can be directly applied to commercial inkjet printers for convenient and high-throughput information encryption on paper.Information was easily printed on different kinds of paper substrates and the information can only be visualized under NIR light excitation.Furthermore,a novel information encryption strategy was designed by utilizing UCNPs with different excitation wavelengths.Only excitation at the defined wavelength can obtain the correct information.This proposed information encryption strategy can completely avoid background fluorescence interference,and it also features easy operation,high throughput as well as low costs,indicating its good promise to serve as a household encryption method in our daily life.
基金supported by the National Natural Science Foundation of China(21871139 and 21975122)Natural Science Foundation of Jiangsu Province,China(BK20191360).
文摘The applications of upconversion nanoparticles in biodetection,bioimaging,and lighting have greatly fuelled a growing demand for enhancing their brightness.The brightness of upconversion nanoparticles is fundamentally limited by the low doping concentration of either activator or sensitizer ions,in spite of the progress of rational controlling nanoparticles to improve performance.Although NaYbF_(4)nano-particles possessing the largest amount of sensitizers(Yb^(3+))have been proposed as a promising alterna-tive host to achieve bright upconversion luminescence,systemic explorations in synthesizing NaYbF_(4)nanoparticles have scarcely been performed.In this work,we report the systematic synthesis and fine control of monodisperse NaYbF_(4)nanoparticles through a canonical high-temperature co-precipitation method.The phase and morphology of NaYbF_(4)nanoparticles can be rationally tuned,through modulat-ing the amount of NH4 F,amount of NaOH,temperature,and time,respectively.The heating rate has also been found to exert an effect on the phase and morphology evolution of NaYbF_(4)nanoparticles for the first time.The size of NaYbF_(4)nanoparticles can be modulated from hundreds to several nanometers,in addition to the variation of their phase and morphology.The optical properties of NaYbF_(4):Er upconver-sion nanoparticles obtained under different reaction parameters have been investigated,and moreover,their potential applications in imaging deep tissue and photodynamic therapy have been explored.Unravelling the phase and morphology evolution of NaYbF_(4)nanoparticles is expected to hold great potential for boosting the brightness of upconversion nanoparticles.
基金the National Natural Science Foundation of China(No.21573185,21773200)the Research Grants Council of Hong Kong (CityU 11204717,11205219).
文摘Lanthanide-doped upconversion nanoparticles are undergoing extensive investigations in many fields,particularly in biophotonics and photophysics.In an attempt to boost upconversion emission intensities,Yb-based fluoride crystals have been recently identified as more efficient alternatives to classical NaYF_(4) crystals.Yb-Based fluoride crystals featuring a maximal occupancy of the host lattice by Yb^(3+)sensitizers facilitate the utilization of excitation light and promote energy transfer to upconverting activators,which contributes to a significant enhancement of upconversion luminescence.In this article,we present a survey of recent studies on chemical preparations of Yb-based fluoride nanoparticles with well-defined size and morphology.We show that these Yb-based upconversion nanoparticles are playing important roles in a few emerging applications such as optogenetics,biodetection and upconversion lasing.
基金supported by the National Natural Science Foundation of China(grant no.NSFC 51720105015,51672269,51929201,51922097,51772124 and 51872282)the Science and Technology Cooperation Project between Chinese and Australian Governments(2017YFE0132300)+5 种基金the Jiangmen Innovative Research Team Program(2017)the Major Program of Basic Research and Applied Research of Guangdong Province(2017KZDXM083)the Key Research Program of Frontier Sciences,CAS(YZDYSSW-JSC018)the Youth Innovation Promotion Association of CAS(grant no.2017273)the Overseas,Hong Kong&Macao Scholars Collaborated Researching Fund(grant no.21728101)the CAS-Croucher Funding Scheme for Joint Laboratories(grant no.CAS18204).
文摘The generation of reactive oxygen species(ROS)is often limited by the overexpression of glutathione(GSH)in the tumor microenvironment(TME)and the penetration depth of visible light.In view of this,we designed biodegradable Cu/ZIF-8 shell-coated lanthanide-doped nanoparticles and loaded with a photosensitizer(Rose Bengal),and fabricated a NIR-triggered nanocomposite NaYF_(4):20%Yb,2%Er@Cu/ZIF-8/RB@F127(UCZRF)for the synergistic treatment of CDT and PDT.Interestingly,the UCZRF nanostructures can specifically release RB and Cu^(2+)in the acidic tumor microenvironment(TME).Cu^(2+)depletes GSH to effectively change the amount of ROS produced by RB under 980 nm laser irradiation,and Cu+from the reduction reaction of GSH reacts with excess hydrogen peroxide(H_(2)O_(2))in the TME to generate hydroxyl radicals(·OH)with high oxidation activity.In such a simple nanosystem,we enhance the anti-tumor effect of CDT and PDT by improving the efficiency of ROS generation.
基金funding from the Swiss National Science Foundation under project number 196971-“Light based Volumetric printing in scattering resins.”。
文摘Light-based additive manufacturing holds great potential in the field of bioprinting due to its exceptional spatial resolution,enabling the reconstruction of intricate tissue structures.However,printing through biological tissues is severely limited due to the strong optical scattering within the tissues.The propagation of light is scrambled to form random speckle patterns,making it impossible to print features at the diffraction-limited size with conventional printing approaches.The poor tissue penetration depth of ultra-violet or blue light,which is commonly used to trigger photopolymerization,further limits the fabrication of high cell-density tissue constructs.Recently,several strategies based on wavefront shaping have been developed to manipulate the light and refocus it inside scattering media to a diffraction-limited spot.In this study,we present a high-resolution additive manufacturing technique using upconversion nanoparticles and a wavefront shaping method that does not require measurement from an invasive detector,i.e.,it is a non-invasive technique.Upconversion nanoparticles convert near-infrared light to ultraviolet and visible light.The ultraviolet light serves as a light source for photopolymerization and the visible light as a guide star for digital light shaping.The incident light pattern is manipulated using the feedback information of the guide star to focus light through the tissue.In this way,we experimentally demonstrate that near-infrared light can be non-invasively focused through a strongly scattering medium.By exploiting the optical memory effect,we further demonstrate micro-meter resolution additive manufacturing through highly scattering media such as a 300-μm-thick chicken breast.This study provides a concept of high-resolution additive manufacturing through turbid media with potential application in tissue engineering.
基金funded by Hong Kong Research Grant Council(GRF14300822)Faculty of Science of the Chinese University of Hong Kong(CRIMS)+1 种基金the Natural Science Foundation of Shandong Province(ZR2023MC178)Youth Innovation Team Development Project of Shandong Province(Food Nanotechnology innovation team).
文摘A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK-CUR-TPP)to enable synergistic tumor therapy via photodynamic(PDT),chemodynamic(CDT),and mild photothermal therapy(mPTT).In this strategy,AuNPs attached to the surface serve as a“pore locker”,cloaking CeO_(2)and CUR before entering tumor cells.UCNPs convert near-infrared(NIR)light into UV and visible light emission,simultaneously initiating AuNP aggregation via photoclick chemistry,CeO_(2)-mediated reactive oxygen species(ROS)generation,and TPP-CUR-driven PDT.The CeO_(2)amplifies oxidative stress by depleting glutathione(GSH)and catalyzing ROS production(O_(2)^(·-)and·OH),while releasing oxygen to relieve tumor hypoxia.The release of TPP-CUR not merely resumes the negativity of the surface,but also disrupts mitochondrial function and downregulates heat shock proteins(HSPs),further sensitizing tumor cells to mPTT(~45℃)performed by light-induced AuNP aggregation after detachment due to electrostatic repulsion.Importantly,ROS-scavenging ability post-PTT of CeO_(2)has been demonstrated to effectively mitigate excessive inflammation and prevent severe scab formation.This fully integrated,lightand ROS-responsive nanoplatform affords significant therapeutic efficacy in 4T1 tumor-bearing BALB/c mice,reducing tumor volume from 185 to 27 mm^(3)following a single tail-vein injection.
基金supported by the grants from the National Natural Science Foundation of China(Grant Nos.52272270,51972084)the Key Technology Research and Industrialization Demonstration Project of Qingdao(Grant No.25-1-1-gjgg-1-gx)+3 种基金the Outstanding Young Scholars Project of the Natural Science Foundation of Heilongjiang Province,China(Grant No.JJ2023JQ0025)the Opening Project of State Key Laboratory of Space Power Sources(Grant No.YF07050123F2531)the Young Scientist Workshop(Harbin Institute of Technology)(Grant No.AUGA5710094420)the Fundamental Research Funds for the Central Universities,China(Grant Nos.AUGA5710052614,HIT.OCEF.2023041).
文摘Optically responsive composite materials hold significant promise for in vivo diagnostics and targeted therapies.Rare-earthdoped upconversion nanoparticles(UCNPs),renowned for their unique luminescence properties,large anti-Stokes shift,excellent biocompatibility,and deep tissue penetration,have emerged as highly promising candidates for advanced phototherapy in biological systems.This review first explores the fundamental mechanisms of upconversion luminescence,as well as synthesis,surface modification,and design strategies to brighten upconversion.It then highlights recent advances and key applications of UCNPs in biological therapy,including upconversion-mediated phototherapy,multimodal therapeutic approaches,and image-guided therapy and surgery.Finally,it discusses the current challenges and opportunities in both fundamental research and clinical translation,providing theoretical insights and practical guidance to support the broader application of UCNPs in biological therapy and clinical medicine.
基金This work was supported by the research start-up fund of Soochow University and the Research Grants Council of Hong Kong SAR(No.CityU5/CRF/08)。
文摘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.
