Despite the large absorption cross-section of Nd3+ dopant as a sensitizer in lanthanide doped luminescence system, the strong cross-relaxation effect of it impedes the promotion of doping concentration and thus reduces the utilization of excitation light. In this work, we introduce a highly efficient acceptor, Yb3+ ion, which can quickly receive energy from Nd3+ ions, to construct an energy transfer highway for the enhancement of near-infrared emission. By using the energy transfer highway, the doping amount of Nd3+ ions in our NaYF4:Yb,Nd@CaF2 core/shell nanoparticles (CSNPs) can be markedly elevated to 60%. The quantum yield of CSNPs was determined to be 20.7%, which provides strong near-infrared luminescence for further bioimaging application. Remarkably, deep tissue penetration depth (∼10 mm) in in vitro imaging and high spatial resolution of blood vessel (∼0.19 mm) in in vivo imaging were detected clearly with weak autofluorescence, demonstrating that probes can be used as excellent NIR biosensors.Keywords: bioimaging; energy transfer; high spatial resolution; Nd3+-sensitized; NIR probe; optimization luminescence;

Nanomedicine has attracted substantial attention for the accurate diagnosis or treatment of carcinoma in recent years. Nd3+-doped lanthanide nanophosphor-based near-infrared-II (NIR-II) optical imaging is widely used for deep penetration tissue imaging while X-ray computed tomography (CT) is well-suited for in vivo imaging. Polymer-coated lanthanide nanophosphors are increasingly used in both diagnostics and therapies for tumor in vivo. However, the biocompatibility of nanocomposites and the efficiency of tumor ablation should be taken into consideration when constructing a nanotheranostic probe. In this article, we have fabricated polydopamine (PDA)-coated NaYF4:Nd3+@NaLuF4 nanocomposites using the reverse microemulsion approach. The thickness of the PDA shell can be precisely modulated from ∼1.5 to ∼18 nm, endowing the obtained NaYF4:Nd3+@NaLuF4@PDA with an excellent colloidal stability and considerable biocompatibility. The photothermal conversion efficiency of the resultant nanocomposites was optimized and maximized by the increase of the PDA shell thickness. Because of the remarkable photothermal conversion efficiency, the mice xenograft tumors were completely eradicated after NIR irradiation. Given the considerable photoluminescence and X-ray attenuation efficiency, the performance of NaYF4:Nd3+@NaLuF4@PDA for NIR-II optical imaging and X-ray CT dual imaging of the tumor in vivo was evaluated. All of the results above highlight the great potential of PDA-based NaYF4:Nd3+@NaLuF4 nanocomposites as a novel multifunctional nanotheranostic agent.Keywords: lanthanide; near-infrared-II; photothermal therapy; polydopamine; X-ray computed tomography;

The development of rare-earth doped upconversion nanoparticles (RE-UCNPs) in various applications is fuelling the demand for nanoparticles with highly enhanced upconversion luminescence (UCL). Although the core/shell structure is proved to enhance the UCL effectively, there is still plenty of room to further improve the UCL by optimizing the doping ratio of the materials. In this article, a general strategy is demonstrated to achieve highly-enhanced visible UCL in core/shell nanostructured NaREF4 by increasing the doping ratio of Yb3+ in the core region. The energy transfer from RE-UCNPs to surface quenching sites through Yb3+–Yb3+ energy migration is demonstrated to be the main reason for restricting the doping ratio of Yb3+. Notable UCL enhancement (ca. 15 times) of core/shell structured α-NaYF4:Yb,Er@CaF2 nanoparticles is observed by increasing the concentration of Yb3+ to 98 mol%. The highly-enhanced visible UCL signal is used to guide the lymphatic vessel resection with the naked eye.

Anti-Stokes shift luminescence is a special optical process, which converts long-wavelength excitation to short-wavelength emission. This unique ability is especially helpful for bio-applications, because the longer-wavelength light source, usually referring to near infrared light, has a larger penetration depth offering a longer working distance for in vivo applications. The anti-Stokes shift luminescence signal can also be distinguished from the auto-fluorescence of biological tissues, thus reducing background interference during bioimaging. Herein, we summarize recent advances in anti-Stokes shift luminescent materials, including lanthanide and triplet–triplet-annihilation-based upconversion nanomaterials, and newly improved hot-band absorption-based luminescent materials. We focus on the synthetic strategies, optical optimization and biological applications as well as present comparative discussions on the luminescence mechanisms and characteristics of these three types of luminescent materials.

In this article, a facile strategy is developed to synthesize a nanocomposite containing both a rare earth doped upconversion nanoparticle (RE-UCNP) and gold nanoparticles (GNPs). Such a nanocomposite can serve as a dual-modal imaging agent for upconversion luminescence (UCL) imaging and photoacoustic tomography (PAT). High spatial resolution, 3-dimensional imaging of blood vessels could be achieved with the RE-UCNP/GNPs@SiO2 nanocomposite by PAT, while UCL imaging offers a high-speed, low-interference and 2-dimensional imaging mode.

The fluorescent probes working in the near-infrared (NIR) window have unparalleled advantages of a high penetration depth and low interference from autofluorescence. In this paper we introduced a rare-earth doped nanoprobe working in this region with a narrow emission band, a high efficiency, and good bio-compatibility. The newly-developed host material LiYF4 managed to strengthen the emission intensity and generate a fine structure of the emission peaks. After the optimization of the doping ratio of Nd3+ and surface modification, the LiYF4:5%Nd3+ probe could reach a penetration depth of 3–5 mm and could be successfully utilized in lymphatic imaging, with a signal-to-noise ratio of 14.8 in vivo and a resolution of ∼0.2 mm in circulatory imaging. This probe may be further used in bio-detection and the host material itself may replace the traditional NaYF4 in some aspects of applications.

Upconversion luminescence nanomaterials have shown great potential in biological and physical applications because of their unique properties. However, limited research exists on the cooperative sensitization upconversion emission in Tb3+ ions over Er3+ ions and Tm3+ ions because of its low efficiency. Herein, by optimizing the doping ratio of sensitizer and activator to maximize the utilization of the photon energy and introducing the CaF2 inert shell to shield sensitizer from quenchers, we synthesize ultrasmall NaYbF4:Tb@CaF2 nanoparticles with a significant enhancement (690-fold) in cooperative sensitization upconversion emission intensity, compared with the parent NaYbF4:Tb. The lifetime of Tb3+ emission in NaYbF4:Tb@CaF2 nanoparticles is prolonged extensively to ∼3.5 ms. Furthermore, NaYbF4:Tb@CaF2 was applied in in vitro and in vivo bioimaging. The presented luminescence enhancement strategy provides cooperative sensitization upconversion with new opportunities for bioapplication.

Lanthanide upconversion nanophosphors (Ln-UCNPs) have attracted great attention in a variety of fields, benefiting from low background fluorescence interference and a high signal-to-noise ratio of upconversion luminescence. However, the establishment of Ln-UCNPs with dual near-infrared (NIR) emission channels still remains challenging. Herein, we report the design and synthesis of Nd3+-sensitized NaYbF4:Tm@NaYF4:Yb@NaNdF4:Yb hierarchical-structured nanoparticles that emit NIR luminescence at 696 and 980 nm under excitation at 808 nm. The sensitizer-rich NaYbF4 core promotes efficient energy transfer to Tm3+. The interlayer of NaYF4:Yb effectively prevents the cross-relaxation process from Tm3+ to Nd3+ and thus enhances the luminescence emission. The introduction of Nd3+ ion as the sensitizer transforms the excitation wavelength from 980 to 808 nm, which subtly averts the laser-induced thermal effect and offers a new pathway for the NIR emission channel at 980 nm. The as-prepared nanoparticles were further applied in developing latent and blood fingerprint images, which exhibited high signal-to-noise ratio and distinguishable details under 808 nm excitation with negligible thermal damage to the sample. Our work provides a promising strategy to realize NIR-to-NIR dual-channel emissions in Ln-UCNPs. With further functionalization, such nanoparticles are expected to have great potential in forensic and biological sciences.

Nitroreductase (NTR) can be overexpressed in hypoxic tumors, thus the selective and efficient detection of NTR is of great importance. To date, although a few optical methods have been reported for the detection of NTR in solution, an effective optical probe for NTR monitoring in vivo is still lacking. Therefore, it is necessary to develop a near-infrared (NIR) fluorescent detection probe for NTR. In this study, five NIR cyanine dyes with fluorescence reporting structure decorated with different nitro aromatic groups, Cy7-1–5, have been designed and explored for possible rapid detection of NTR. Our experimental results presented that only a para-nitro benzoate group modified cyanine probe (Cy7-1) could serve as a rapid NIR fluorescence-enhanced probe for monitoring and bioimaging of NTR. The structure–function relationship has been revealed by theoretical study. The linker connecting the detecting and fluorescence reporting groups and the nitro group position is a key factor for the formation of hydrogen bonds and spatial structure match, inducing the NTR catalytic ability enhancement. The in vitro response and mechanism of the enzyme-catalyzed reduction of Cy7-1 have been investigated through kinetic optical studies and other methods. The results have indicated that an electro-withdrawing group induced electron-transfer process becomes blocked when Cy7-1 is catalytically reduced to Cy7-NH2 by NTR, which is manifested in enhanced fluorescence intensity during the detection process. Confocal fluorescence imaging of hypoxic A549 cells has confirmed the NTR detection ability of Cy7-1 at the cellular level. Importantly, Cy7-1 can detect tumor hypoxia in a murine hypoxic tumor model, showing a rapid and significant enhancement of its NIR fluorescence characteristics suitable for fluorescence bioimaging. This method may potentially be used for tumor hypoxia diagnosis.

Excessive or misplaced production of ClO− in living systems is usually associated with many human diseases. Therefore, it is of great importance to develop an effective and sensitive method to detect ClO− in living systems. Herein, we designed an 808 nm excited upconversion luminescence nanosystem, composed of the Nd3+-sensitized core–shell upconversion nanophosphor NaYF4:30%Yb,1%Nd,0.5%Er@NaYF4:20%Nd, which serves as an energy donor, and the ClO−-responsive cyanine dye hCy3, which acts as an energy acceptor, for ratiometric upconversion luminescence (UCL) monitoring of ClO−. The detection limit of ClO− for this nanoprobe in aqueous solution is 27 ppb and the nanoprobe was successfully used to detect the ClO− in the living cells by ratiometric upconversion luminescence. Importantly, the nanoprobe realized the detection of ClO− in a mouse model of arthritis, which produced an excess of ROS, under 808 nm irradiation in vivo. The excitation laser efficiently reduced the heating effect, compared to the commonly used 980 nm laser for upconversion systems.

Cysteine (Cys) plays crucial roles in biological systems and in mitochondrial processes. Highly selective probes for specific detection of mitochondrial Cys over other biological thiols are rare. Herein, we designed and synthesized a mitochondria-targetable near-infrared (NIR) fluorescent off–on probe, NFL1, based on a fluorescein derivative for Cys detection. Probe NFL1 has a lipophilic cation unit as the mitochondria biomarker and an acrylate group as the Cys-recognition unit as well as a fluorescence quencher. The probe itself is nonfluorescent due to the photoinduced electron transfer process. Upon addition of Cys, marked enhancement in the NIR emission (735 nm) can be monitored due to cleavage of the acrylate moiety. This probe had great sensitivity and selectivity for the rapid detection of Cys over homocysteine (Hcy) and glutathione (GSH) with an ultralow detection limit of 14.5 nM. More importantly, the probe successfully targeted mitochondria, detected endogenous Cys, and assessed mitochondrial oxidative stress in living cells. Probe NFL1 was also capable of detecting and imaging Cys in living nude mice, indicating its significant potential in biological applications.Keywords: cysteine; fluorescent probe; imaging; mitochondria-targeted; near-infrared

Upconversion detection nanocomposites were assembled for the selective luminescent detection of mercury ions in water. A hydrophobic cyclometallated ruthenium complex [RuII(bpy)2(thpy)]PF6 (abbreviated as Ru1; bpy = 2,2′-bipyridine and thpy = 2-(2-thienyl)pyridine) is employed as a chemodosimeter to assemble on amphiphilic polymer-coating upconversion nanophosphors (UCNPs) based on the hydrophobic–hydrophobic interaction. Upon addition of Hg2+, the nanocomposite not only exhibits a remarkable color change from deep-red to yellow, but also an enhanced upconversion luminescence (UCL) emission by hindering the luminescent resonance energy transfer (LRET) process from the upconversion emission of UCNPs to Ru1. Using the ratiometric UCL emission as a detection signal, the detection limit of Hg2+ for this nanoprobe in aqueous solution is 8.2 ppb, which is much lower than that (329 ppb) determined by UV/Vis technology. Such an Hg2+-tunable LRET process provides a general strategy for fabricating a water-soluble upconversion-based nanoprobe for some special analyte.

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

An N719 functionalized magnetic silica yolk–shell nanocomposite was synthesized, and its applications in the sensing and removal of mercury ions were evaluated by optical titration experiments and ICP. Using the ratiometric absorbance as a detection signal, the detection and removal of Hg2+ was realized in water.

Upconversion nanophosphors (UCNPs) have been widely used in bioscience and bioimaging, but the effect of UCNPs on plants and on animals after subsequent oral ingestion of the plants has not been studied previously. Herein, we investigate the effects of UCNPs on plant development using mung beans as a model. Incubation at a high UCNP concentration of 100 μg/mL led to growth inhibition, while a low concentration of 10 μg/mL promoted their development. Confocal imaging showed that UCNPs accumulated in the seeds and were transferred from seeds and roots to stems and leaves through the vascular system. Quantitative study by radioanalysis showed the distribution of UCNPs in the plant on the 5th day after incubation decreased in the order (root > seed > leaf > stem). After UCNP-treated bean sprouts were orally ingested by mice, UCNPs were completely excreted with feces, without absorption of residual amounts. Histology and hematology results showed no detectable toxic effects of UCNP-treated mung beans on exposed mice.

Anti-Stokes shift luminescence is a special optical process, which converts long-wavelength excitation to short-wavelength emission. This unique ability is especially helpful for bio-applications, because the longer-wavelength light source, usually referring to near infrared light, has a larger penetration depth offering a longer working distance for in vivo applications. The anti-Stokes shift luminescence signal can also be distinguished from the auto-fluorescence of biological tissues, thus reducing background interference during bioimaging. Herein, we summarize recent advances in anti-Stokes shift luminescent materials, including lanthanide and triplet–triplet-annihilation-based upconversion nanomaterials, and newly improved hot-band absorption-based luminescent materials. We focus on the synthetic strategies, optical optimization and biological applications as well as present comparative discussions on the luminescence mechanisms and characteristics of these three types of luminescent materials.

The fluorescent probes working in the near-infrared (NIR) window have unparalleled advantages of a high penetration depth and low interference from autofluorescence. In this paper we introduced a rare-earth doped nanoprobe working in this region with a narrow emission band, a high efficiency, and good bio-compatibility. The newly-developed host material LiYF4 managed to strengthen the emission intensity and generate a fine structure of the emission peaks. After the optimization of the doping ratio of Nd3+ and surface modification, the LiYF4:5%Nd3+ probe could reach a penetration depth of 3–5 mm and could be successfully utilized in lymphatic imaging, with a signal-to-noise ratio of 14.8 in vivo and a resolution of ∼0.2 mm in circulatory imaging. This probe may be further used in bio-detection and the host material itself may replace the traditional NaYF4 in some aspects of applications.