Lanthanide-doped rare earth nanoparticles for nearinfrared-Ⅱimaging and cancer therapy

The optical nanoprobes with emissions in the second near-infrared window(NIR-Ⅱ,1000-1700 nm)show low tissue autofluorescence and photon scattering;therefore,they provide high spatial resolution and acceptable tissue penetration depth.These advantages make them appropriate for in vivo applications,including bioimaging,NIR-Ⅱtriggered disease therapy,and even on-site efficacy monitoring.Among the various developed NIR-Ⅱfluorescence probes,lanthanide-doped nanoparticles(LDNPs)exhibit high photo stability and narrow emission bandwidths with long photoluminescence lifetimes and low cytotoxicity;therefore,they have been widely studied in the biomedical field.This review summarizes the typical compositions and optical properties of recently developed NIR-Ⅱemitting LDNPs.Their applications in in vivo NIR-Ⅱbioimaging and cancer therapy are reviewed.The perspectives and challenges of NIR-ⅡLDNPs are also discussed.

Research Article Acetic acid-mediated rapid cubic-to-hexagonal(α-β)phase transformation for ultra-bright lanthanide-dopedβ-NaYF_(4)nanobioprobes

Hexagonal-phase NaYF_(4)(β-NaYF_(4))has been acknowledged to be one of the most efficient doping hosts to prepare bright lanthanide-doped luminescent nano-bioprobes for various biomedical applications.However,to date,it remains a great challenge to synthesize ultra-bright lanthanide-dopedβ-NaYF_(4)nano-bioprobes under a low reaction temperature by using conventional synthetic methods.Herein,we first develop an acetic acid(HAc)-mediated coprecipitation method for the preparation of ultrabright lanthanide-dopedβ-NaYF_(4)nanoprobes under a low reaction temperature at 200℃.Based on a series of comparative spectroscopic investigations,we show that the use of HAc in the reaction environment can not only promote the rapidα-βphase transformation of NaYF_(4)host at 200℃ within 1 h but also boost the absolute photoluminescence quantum yield(PLQY)of NaYF_(4)nanocrystals to 30.68%for near-infrared emission and to 3.79%for upconversion luminescence,both of which are amongst the highest values for diverse lanthanide-doped luminescent nanocrystals ever reported.By virtue of their superior nearinfrared luminescence,we achieve optical-guided dynamic vasculature imaging in vivo of the whole body at a high spatial resolution(23.8μm)under 980 nm excitation,indicating its potential for the diagnosis and treatment evaluation of vasculaturerelated diseases.

"Chameleon-like" optical behavior of lanthanide-doped fluoride nanoplates for multilevel anti-counterfeiting applications

Lanthanide-based luminescent anti-counterfeiting materials are widely used in various kinds of products.However,the emission color of traditional lanthanide-based luminescent materials usually remains nearly unaltered upon different excitation lights,which may only work for single-level anti-counterfeiting.Herein,the NaYbF4∶2%Er@NaYF4 core/shell nanoplates (NPs) with "chameleon-like" optical behavior are developed.These NPs display single-band red or green downshifting (DS) emission upon excitation at 377 or 490 nm,respectively.Upon 980 nm excitation,the color of upconversion (UC) emission can be finely tuned from green to yellow,and to red with increasing the excitation power density from 0.1 to 4.0 W/cm^2.The proposed materials readily integrate the advantages of excitation wavelength-dependent DS single-band emissions and sensitive excitation power-dependent UC multicolor emissions in one and the same material,which has never been reported before.Particularly,the proposed NPs exhibit excellent performance as security labels on trademark tag and security ink on painting,thus revealing the great potential of these lanthanide-doped fluoride NPs in multilevel anti-counterfeiting applications.

A facile ＂ship-in-a-bottle＂ approach to construct nanorattles based on upconverting lanthanide-doped fluorides

Rattle structure is a topic of great interest in design and application of nano- materials due to the unique core@void@shell architecture and the integration of functions. Herein, we developed a novel ＂ship-in-a-bottle＂ method to fabricate upconverting （UC） luminescent nanorattles by incorporating lanthanide-doped fluorides into hollow mesoporous silica. The size of nanorattles and the filling amount of fluorides can be well controlled. In addition, the modification of silica shell （with phenylene and amine groups） and the variation of efficient UC fluorides （NaYF4：Yb, Er, NaLuF4：Yb, Er, NaGdF4：Yb, Er and LiYF4：Yb, Er） were readily achieved. The resulting nanorattles exhibited a high capacity and pH-dependent release of the anti-cancer drug doxorubicin （DOX）. Furthermore, we employed these nanorattles in proof-of-concept UC-monitoring drug release by utilizing the energy transfer process from UC fluorides to DOX, thus revealing the great potential of the nanorattles as efficient cancer theranostic agent.

Temperature modulation of concentration quenching in lanthanide-doped nanoparticles for enhanced upconversion luminescence

The doping concentration of lanthanide ions is important for manipulating the luminescence properties of upconversion nanoparticles （UCNPs）. However, the serious concentration quenching in highly doped UCNPs remains a vital restriction for further enhanced upconversion luminescence （UCL）. Herein, we examined the effect of temperature on the concentration quenching of rare-earth UCNPs, an issue that has been overlooked, and we show that it is significant for biomedical or optical applications of UCNPs. In this work, we prepared a series of UCNPs by doping Er3. luminescent centers at different concentrations in a NaLuF4：Yb3＋ matrix. At room temperature （298 K）, steady-state photoluminescence （PL） spectroscopy showed substantial concentration quenching of the Er~ emission with increasing doping concentrations. However, the concentration quenching effect was no longer effective at lower temperatures. Kinetic curves obtained from time-resolved PL spectroscopy further showed that the concen- tration quenching dynamics were vitally altered in the cryogenic temperature region, i.e., below 160 K. Our work on the temperature-switchable concentration quenching mechanism may shed light on improving UCL properties, promoting their practical applications.

Lanthanide-doped metal-organic frameworks with multicolor mechanoluminescence

Metal-organic frameworks(MOFs)and mechanoluminescent(ML)materials have been considered as two types of promising materials that have their own application fields.It would be amazing to endow one material with the advantages of ML and MOFs,thus broadening their applications.However,there are quite few investigations on this topic,and the ML mechanism in ML-MOFs remains unclear.In this study,we proposed a strategy for developing ML-MOFs by doping lanthanide ions into the non-centrosymmetric SBD([Sr(μ-BDC)(DMF)]∞)MOF,and successfully synthesized a series of lanthanide-doped MOFs Ln-SBD(Ln=Tb,Dy,Sm,Eu)and Tb1-xEux-SBD(x=0.2,0.4,0.6,0.8)with multicolor ML.The lanthanide ions were uniformly distributed in the matrix of the SBD-MOF,and occupied the Sr site.The MLMOFs exhibited intense multicolor ML emissions varying from green to yellow to red by changing the co-doping ratios and species of lanthanide ions.The similar ML and photoluminescence(PL)spectra indicated that the ML emission was assigned to the radiative transition from the excited states to the ground states of lanthanide ions.The radiative transition was induced by the electron bombardment process that originated from the piezoelectric effect of the non-centrosymmetric SBD host.In addition,a pioneering temperature sensing research based on ML was carried out,which is promising for realizing dual-functional detection of stress and temperature without excitation light sources.This study gives a unique insight for developing more versatile and interesting smart materials by combining the versatility of MOF with the ML emission,imparting additional values to both MOF and ML materials.Moreover,this study provides a general rule for selecting MOFs with an acentric structure as the host for ML materials.

Preparation of NaYF4:Yb^3+,Tm^3+@NaGdF4:Ce^3+,Eu3+double-jacket microtubes for dual-mode fluorescent anti-counterfeiting

Novel hydrophilic NaYF4:Yb^3+,Tm^3+@NaGdF4:Ce^3+,Eu^3+double-jacket microtubes(DJMTs)with upconversion/downconversion dual-mode luminescence were designed and prepared through epitaxial growth of NaGdF4:Ce^3+,Eu^3+shell onto the NaYF4:Yb^3+,Tm^3+microtube via poly(acrylic acid)(PAA)mediated hydrothermal method.It is demonstrated that PAA ligand played an important role in guiding the direct growth of NaGdF4:Ce^3+,Eu^3+shell onto the surface of NaYF4:Yb^3+,Tm^3+parent microtubes.The growth of NaGdF4:Ce^3+,Eu^3+shell experienced a crystal phase transition fromβ-NaGdF4 andβ-NaYF4 mixture toβ-NaYF4@NaGdF4 composite crystal,and morphology evolution from mixture ofβ-NaGdF4:Ce^3+,Eu^3+nanorods andβ-NaYF4:Yb^3+,Tm^3+microtubes to NaYF4:Yb^3+,Tm^3+@NaGdF4:Ce^3+,Eu^3+DJMTs.The formation mechanism of DJMTs was the dissolution−renucleation ofβ-NaGdF4:Ce^3+,Eu^3+nanorods and the growth ofβ-NaGdF4:Ce^3+,Eu^3+shell via the classical Ostwald ripening mechanism.The as-prepared DJMTs could exhibit blue upconversion and red downconversion luminescence,which was further made into environmentally benign luminescent inks for creating highly secured and fluorescent-based anti-counterfeiting patterns via inkjet printing.

具有红色上转换发光和近红外二区发光的生物可降解镧系掺杂无机纳米颗粒用于生物成像和光动力治疗

近红外二区镧掺杂无机纳米颗粒由于其较低的光子散射和较弱的自身荧光特性而受到广泛关注.然而,这些纳米颗粒具有“刚性”和生理惰性的晶格结构(例如NaYF_(4):Yb,Er),无法在体内降解,限制了它们在生物医学上的进一步应用.改变化学结构,实现晶体由“刚性”向“软性”的转变,是一种促进其可降解生物应用的可行方法.在这里,我们报道了一种可生物降解的近红外二区镧掺杂无机纳米颗粒Na_(3)ZrF_(7):Yb,Er,Ce(NZF).通过Na的调控和Ce^(3+)的掺杂优化,NZF纳米粒子的近红外二区下转换发光强度比Na_(3)ZrF_(7):Yb,Er提高了约37倍.由于其“软”的晶格特征,水可以破坏其晶体结构,降解产物可以从器官和组织中排出.此外,NZF还表现出红色的上转换发光能力.在表面改性后,我们基于其近红外二区的下转换发光和红色上转换发光的特性进行了可降解生物成像应用和光动力治疗的概念验证,这些发现将有利于稀土掺杂无机纳米颗粒的未来生物医学应用.

Up-converting NaYF4:0.1%Tm^(3+), 20%Yb^(3+) nanoparticles as luminescent labels for deep-tissue optical imaging

Optical imaging plays an important role in biomedical research being extremely useful for early detection, screening and image-guided therapy. Lanthanide-doped up-converting nanoparticles were ideally suited for bioimaging because they could be ex- cited in near infrared （NIR） and emit in NIR or visible （VIS）. Here, we compared lanthanide doped up-converting NaYF4 and organic fluorophores for application in deep-tissue imaging. For that purpose - tissue phantoms mimicking the natural properties of light scat- tering by living tissues were prepared. The studies allowed to quantitatively compare optical resolution of different fluorescent com- pounds, revealing that the NIR photoexcitation was favorable over conventional UV photoexcitation.

Plasmonic enhancement and polarization dependence of nonlinear upconversion emissions from single gold nanorod@SiO_(2)@CaF2:Yb^(3+),Er^(3+)hybrid core–shell–satellite nanostructures

Lanthanide-doped upconversion nanocrystals(UCNCs)have recently become an attractive nonlinear fluorescence material for use in bioimaging because of their tunable spectral characteristics and exceptional photostability.Plasmonic materials are often introduced into the vicinity of UCNCs to increase their emission intensity by means of enlarging the absorption cross-section and accelerating the radiative decay rate.Moreover,plasmonic nanostructures(e.g.,gold nanorods,GNRs)can also influence the polarization state of the UC fluorescence—an effect that is of fundamental importance for fluorescence polarization-based imaging methods yet has not been discussed previously.To study this effect,we synthesized GNR@SiO_(2)@CaF2:Yb^(3+),Er^(3+)hybrid core–shell–satellite nanostructures with precise control over the thickness of the SiO_(2) shell.We evaluated the shell thicknessdependent plasmonic enhancement of the emission intensity in ensemble and studied the plasmonic modulation of the emission polarization at the single-particle level.The hybrid plasmonic UC nanostructures with an optimal shell thickness exhibit an improved bioimaging performance compared with bare UCNCs,and we observed a polarized nature of the light at both UC emission bands,which stems from the relationship between the excitation polarization and GNR orientation.We used electrodynamic simulations combined with Förster resonance energy transfer theory to fully explain the observed effect.Our results provide extensive insights into how the coherent interaction between the emission dipoles of UCNCs and the plasmonic dipoles of the GNR determines the emission polarization state in various situations and thus open the way to the accurate control of the UC emission anisotropy for a wide range of bioimaging and biosensing applications.

Rational design and biomedical applications of DNA-functionalized upconversion nanoparticles

Lanthanide-doped upconversion nanoparticles （UCNPs） offer unique advantages in term of low autofluorescence, high signal-to-noise ratio and deep tissue penetration, and have attracted considerable attention in biomedical applications. DNA, beyond the properties of self-assembly, also exhibits multiple functions such as molecular recognition, drug loading capacity and therapeutic effect. In this regard, the combination of UCNPs and DNA offers a promising and powerful platform for potential applications in biosensing, bioimaging and disease therapy. In this review, we mainly introduce recent progresses of DNA-functionalized upconversion materials, providing an overview of the design and applications in biosensing, bioimaging and therapy. The challenges and future perspectives are also discussed, aiming to promote their applications in material science and biomedicine.

Luminescence interference-free lifetime nanothermometry pinpoints in vivo temperature

Luminescence nanothermometry makes non-invasive and real-time temperature readings possible in living animals.However,the spectral fluctuation in tissues and fluids,as well as the interaction between fluorophores and environment hinders accuracy of the thermometry.Here,we report a luminescence lifetime-based nanothermometry which specifically addresses this problem.A temporal based calibration(lifetime sensing)in the NIR range,an endogenous thermal response as well as a polymer encapsulation evading environmental factors,altogether help to pinpoint temperature in vivo.Thanks to the highly condensed NdYb ions in a well-protected tiny core-shell nanocrystal(overall 11 nm),a temperature sensitivity about 2.07%K^(-1)(with 5%Yb^(3+)doped nanoparticles)and an accuracy of 0.27 K(with 25%Yb^(3+)doped nanoparticles)in biological fluids are achieved.Hopefully,combining thermally activated energy transfer nanothermometer with anti-interference lifetime thermometry would provide a more accurate temperature measurement for biological and preclinical studies.

Luminescent nano-bioprobes based on NIR dye/lanthanide nanoparticle composites

Near-infrared(NIR)light,which has ignorable tissue scattering/absorption,minimal photodamage,and no autofluorescence interference,is highly favorable for bioapplications.NIR dye and lanthanide-doped nanoparticle(LnNP),as representative NIR-excited luminescence probes,have attracted increasing interest due to their unique optical property and low biological toxicity.Design of luminescence probes based on NIR dye/LnNP nanocomposites cannot only integrate the advantages but also achieve additional functions via regulating internal energy transfer pathways.In this review,we focus on the most recent advances in the development of NIR dye/LnNP nanocomposites as potential bioprobes,which cover from their fundamental photophysics to bioapplications,including energy transfer mechanisms,interface engineering(involving binding interaction,distance,and aggregation as key factors),and their applications for dye-sensitized upconversion/downshifting luminescent bioimaging,detection of biomolecules,and NIR-triggered diagnosis and therapy.Some future prospects and efforts toward this active research field are also envisioned.