Ultrasmall Upconversion Nanoparticles Research Articles

Transient energy trapping as a size-conserving surface passivation strategy for producing bright ultrasmall upconversion nanoprobes

Lanthanide-doped upconversion nanoparticles (UCNPs) have been widely exploited as nanoprobes or energy transducers in traditional as well as emerging biological applications, such as bioimaging, photodynamic therapy, optogenetics, gene editing. However, the breadth and depth of their utility in the biomedical areas are still not comparable to conventional luminescent probes, such as fluorescent dyes and semiconductor quantum dots. Their application is largely limited by their large size, typically > 20 nm, to ensure a sufficient luminescence brightness. In order to enhance the brightness of UCNPs without exceeding the critical size limitations for biomedical applications, we employ here a transient energy trapping effect as a nanoprobe surface passivation strategy to prevent deleterious distant energy migration in the host lattice, which is particularly prevalent in ultrasmall UCNPs and leads to luminescence quenching. We demonstrate this strategy by incorporating Tm3+ ions as energy trapping centers near the surface of sub-10 nm NaYF4: Yb, Er UCNPs and obtain an emission enhancement by almost one order of magnitude without any increment on the nanoparticle size. Our work presents a promising strategy for the preparation of ultrasmall and bright upconversion nanoprobes that are less vulnerable to surface quenching and that potentially minimize the interference with the object. This facilitates their biomedical applications as here demonstrated by unprecedented high-quality cell labeling and imaging, featured with very uniform nanoparticle distribution in the outer nuclear region.

Optimizing the performance of dye-sensitized upconversion nanoparticles

Upconversion nanoparticles (UCNPs) are promising for bioimaging, sensing, and other applications, but their upconversion (UC) efficiency is far from satisfactory. Organic dye sensitization is considered to be an effective strategy to improve the performance of UCNPs. In this work, we provide direct evidence that organic sensitizer surpasses inorganic sensitizer in sensitization capability. To maximize the performance of dye-sensitized UCNPs, three critical factors, namely different optically inert lanthanide ions, Yb3+ doping concentration, and particle size, are systemically investigated and optimized. It is found that the optimal Yb3+ doping concentration and particle size are determined to be 20% and ~19 nm for dye-sensitized UCNPs, while different optically inert lanthanide ions have negligible influence on this system. Importantly, our results suggest that dye sensitization is more favorable for improving the performance of smaller-sized UCNPs. Although ultrasmall UCNPs (<10 nm) are desirable for biomedical applications UCNPs due to their reduced toxicity, they suffer from extremely low UC efficiency and weak brightness. Fortunately, the strategy of dye sensitization turns out to be particularly useful for producing ultrasmall and ultrabright UCNPs, which are desirable for biomedical applications.

Photo-physical studies of ultrasmall upconversion nanoparticles embedded organometallic complexes: Probing a dual mode optical sensor for hydrogen peroxide

Here, we report an upconversion nanoparticles (UCNPs) embedded organomettalic complex for detection of hydrogen peroxide (H2O2). The structural as well as the optical properties of the hybrid nanoparticles (HNPs) have been studies to confirm the interaction as well as energy transfer mechanism. The structural characterization confirm the weak interacting force between the UCNPs and the organic complex in HNPs. The optical studies reveal that, HNPs show characteristic optical behaviour of both the phases i.e. it gives an intense downconverted red emission under UV excitation, due to the presence of organic part (Eu3+ ion) as well as an efficient blue upconverted emission from inorganic part (Tm3+ ion) under NIR excitation. The energy transfer between the inorganic (Tm3+ ion) and the organic (Eu3+ ion) material has been observed, which confirms the effective attachment of both the phases in HNPs. The upconversion and downconversion emission properties, have been have successfully utilized for dual mode H2O2 detection.

Degradable magnetic-response photoacoustic/up-conversion luminescence imaging-guided photodynamic/photothermal antitumor therapy.

In this research, a degradable uniform mesoporous platform was designed as an imaging-guided photothermal therapy (PTT)/photodynamic therapy (PDT) agent. Fe3O4 nanoparticles were prepared using the solvothermal method, and a layer of mesoporous SiO2 was coated onto them using sol-gel and etching processes, then these ultra-small up-conversion nanoparticles (UCNPs) were loaded into the porous structure through electrostatic conjunction and physical absorption. By adjusting the etching processes, Fe3O4@mSiO2 and mSiO2 with a high surface area as a carrier host could be obtained separately. Importantly, the platform could recognize the tumor cells with a magnetic-response and then present strong photoacoustic (PA) and up-conversion luminescence (UCL) signals, and Fe3O4@mSiO2 as drug carriers could be degraded by hydrolysis. Furthermore, under a single 808 nm laser, the temperature of Fe3O4@mSiO2@UCNPs rises much higher than that of the surrounding tissues, and produces a large amount of singlet oxygen because a strong crossover occurs between the emitted blue emission of the UCNPs and the absorbance region of Fe3O4. Therefore, the Fe3O4@mSiO2@UCNPs can be used as a magnetic-targeted dual-modal imaging guided PTT/PDT theranostic probe.

Activation of the surface dark-layer to enhance upconversion in a thermal field

Thermal quenching, in which light emission experiences a loss with increasing temperature, broadly limits luminescent efficiency at higher temperature in optical materials, such as lighting phosphors1–3 and fluorescent probes4–6. Thermal quenching is commonly caused by the increased activity of phonons that leverages the non-radiative relaxation pathways. Here, we report a kind of heat-favourable phonons existing at the surface of lanthanide-doped upconversion nanomaterials to combat thermal quenching. It favours energy transfer from sensitizers to activators to pump up the intermediate excited-state upconversion process. We identify that the oxygen moiety chelating Yb3+ ions, [Yb···O], is the key underpinning this enhancement. We demonstrate an approximately 2,000-fold enhancement in blue emission for 9.7 nm Yb3+-Tm3+ co-doped nanoparticles at 453 K. This strategy not only provides a powerful solution to illuminate the dark layer of ultra-small upconversion nanoparticles, but also suggests a new pathway to build high-efficiency upconversion systems.

Y1-receptor-ligand-functionalized ultrasmall upconversion nanoparticles for tumor-targeted trimodality imaging and photodynamic therapy with low toxicity.

Achieving efficient photodynamic therapy (PDT) in deeper biological tissue is still the biggest bottleneck that limits its widespread application in clinic. Although deeper biological tissue PDT could be realized through a combination of upconversion nanoparticles with a photosensitizer, issues with particle-size-induced upconversion fluorescence (UF) reduction and the related in vivo toxicity still cannot be solved properly. In this study, we synthesized Y1Rs-ligand [Pro30, Nle31, Bpa32, Leu34]NPY(28-36) (NPY)-modified and photosensitizer MC540-loaded LiLuF4:Yb,Er@nLiGdF4@mSiO2 multifunctional nanocomposites (MNPs) with a core-multishell structure and ultrasmall size. Their in vitro and in vivo breast tumor targeting, trimodality imaging performance, PDT therapeutic efficacy, and acute toxicity were evaluated. Our results demonstrated that the core-multishell MNPs(MC540) could achieve excellent UF imaging, and that doping with Gd3+ and Lu3+ rare earth ions could enhance the MR and CT imaging performance. In addition, the mSiO2 shell provided a higher loading rate for the photosensitizer MC540, and the DSPE-PEG thin layer coating outside the MNPs(MC540) further improved the water solubility and biocompatibility, reducing the acute toxicity of the nanocomposites. Finally, the NPY modification enhanced the targetability of MNPs(MC540)/DSPE-PEG-NPY to breast tumors, improving the trimodality UF, CT, and MR imaging performance and PDT efficacy for Y1-receptor-overexpressed breast cancer. In general, our developed multifunctional nanocomposites can serve as a theranostic agent with low toxicity, providing great potential for their use in clinical breast cancer diagnosis and therapy.

A Core-Shell-Satellite Structured Fe3 O4 @g-C3 N4 -UCNPs-PEG for T1 /T2 -Weighted Dual-Modal MRI-Guided Photodynamic Therapy.

Reactive oxygen species (ROS) produced in the specific tumor site plays the key role in photodynamic therapy (PDT). Herein, a multifunctional nanoplatform is designed by absorbing ultrasmall upconversion nanoparticles (UCNPs) on mesoporous graphitic-phase carbon nitride (g-C3 N4 ) coated superparamagnetic iron oxide nanospheres, then further modified with polyethylene glycol (PEG)molecules (abbreviated as Fe3 O4 @g-C3 N4 -UCNPs-PEG). The inert g-C3 N4 layer between Fe3 O4 core and outer UCNPs can substantially depress the quenching effect of Fe3 O4 on the upconversion emission. Upon near-infrared (NIR) laser irradiation, the UCNPs convert the energy to the photosensitizer (g-C3 N4 layer) through fluorescence resonance energy transfer process, thus producing a vast amount of ROS. In vitro experiment exhibits an obvious NIR-triggered cell inhibition due to the cellular uptake of nanoparticles and the effective PDT efficacy. Notably, this platform is responsive to magnetic field, which enables targeted delivery under the guidance of an external magnetic field and supervises the therapeutic effect by T1 /T2 -weighted dual-modal magnetic resonance imaging. Moreover, in vivo therapeutic effect reveals that the magnetism guided accumulation of Fe3 O4 @g-C3 N4 -UCNPs-PEG can almost trigger a complete tumor inhibition without any perceived side effects. The experiments emphasize that the excellent prospect of Fe3 O4 @g-C3 N4 -UCNPs-PEG as a magnetic targeted platform for PDT application.

Enhanced high-order ultraviolet upconversion luminescence in sub-20 nm β-NaYbF4:0.5% Tm nanoparticles via Fe3+doping

Despite showing great promise in bioapplications, lanthanide-doped upconversion nanoparticles (UCNPs) are still restricted by low upconversion efficiency. In this work, ultra-small, monodisperse and uniform β-NaYbF4:0.5% Tm NPs were successfully prepared through a solvothermal route, and remarkably enhanced ultraviolet upconversion luminescence (UV UCL) had been achieved via Fe3+ doping. The UV UCL enhancement in NaYbF4:0.5% Tm NPs was investigated in detail. It was found that the UCL intensities of the UV and blue emissions of NPs doped with 5 mol% Fe3+ ions were enhanced by 10 and 6 times, respectively, compared to that of the Fe3+-free sample. The enhancement of UV UCL is mainly ascribed to the high population density of excited Yb3+ and the energy transfer from |2F7/2, 4T1g > (Yb3+–Fe3+ dimer) to 3F2,3 (Tm3+) states. Moreover, through dynamic analysis, we further demonstrate the proposed mechanisms of UC processes. The results suggest that ultra-small UCNPs with enhanced UV UCL may have potential applications in the biomedical field.

Synthesis, multicolour tuning, and emission enhancement of ultrasmall LaF3:Yb3+/Ln3+ (Ln = Er, Tm, and Ho) upconversion nanoparticles

The development of efficient sub-10 nm ultrasmall upconversion nanoparticles will open the door to the exciting application in biological labelling and imaging. In this paper, we demonstrated a facile method for the synthesis of monodisperse sub-10 nm hexagonal-phased LaF3 nanoparticles doped with upconverting lanthanide ions (Yb3+/Ln3+, Ln = Er3+, Tm3+, and Ho3+). The particle size of the as-synthesized LaF3 nanoparticles can be tuned by varying the preparation temperature. Upon excitation at 980 nm, the LaF3:Yb3+/Ln3+ nanoparticles showed intense upconversion emissions, and the colour output can be precisely modulated by changing the species and concentration of the lanthanide activators. In order to further enhance the upconversion emission intensity of the ultrasmall LaF3:Yb3+/Ln3+ nanoparticles, we adopted the strategy of core–shell nanostructured design to minimize the surface quenching effect. After coating an inert LaF3 shell, a maximum ninefold enhancement in upconversion luminescence was achieved under 980 nm excitation. These as-prepared lanthanide-doped LaF3 upconversion nanoparticles may find promising applications in biomedicine fields as luminescent nanoprobes.

Controlled synthesis of ultrasmall hexagonal NaTm0.02Lu0.98−xYbxF4 nanocrystals with enhanced upconversion luminescence

Ultrasmall upconversion (UC) nanoparticles with intense luminescence are quite desirable for in vitro and in vivo bioimaging. Herein, we report the successful synthesis of sub-10 nm hexagonal NaTm0.02Lu0.98−xYbxF4 nanocrystals via a high boiling solvent process. The sizes and phases of the crystals can be finely tailored by tuning the amounts of the ligands used (octadecylamine and sodium oleate) and the temperature. The intensity of the UC emission of the nanocrystals increases as the the relative content of Yb3+ ions increases from 20% to 98%, owing to improved near-infrared absorption and energy-transfer from Yb3+ to Tm3+. The experimental results indicate that hexagonal NaYbF4 is the best host for ultrasmall Tm3+-doped UC nanoparticles and shows great potential in biomedical applications.