Near-Infrared Light-Excited Reactive Oxygen Species Generation by Thulium Oxide Nanoparticles.

Exploring materials that can absorb near-infrared (NIR) light to produce reactive oxygen species (ROS) is necessary for many fields. Herein we show that thulium oxide nanoparticles are viable for NIR-stimulated ROS generation. This property may be related to the unique energy levels, large absorption cross section, low fluorescence emission, and ∼10-3 s lifetime of the 3H4 state of Tm ions. We further demonstrate the impact of these nanoparticles on photodynamic therapy (PDT), in which impressive tumor inhibition was recorded after exposure to either a broadband halogen lamp or an 808 nm laser. Our results may provide insight into the areas of photocatalysis, pollution treatment, and fine chemical synthesis.

Upconversion-nanoparticle-functionalized Janus micromotors for efficient detection of uric acid.

We report enzyme-powered upconversion-nanoparticle-functionalized Janus micromotors, which are prepared by immobilizing uricase asymmetrically onto the surface of silicon particles, to actively and rapidly detect uric acid. The asymmetric distribution of uricase on silicon particles allows the Janus micromotors to display efficient motion in urine under the propulsion of biocatalytic decomposition of uric acid and simultaneously detect uric acid based on the luminescence quenching effect of the UCNPs modified on the other side of SiO2. The efficient motion of the motors greatly enhances the interaction between UCNPs and the quenching substrate and improves the uric acid detection efficiency. Overall, such a platform using uric acid simultaneously as the detected substrate and motion fuel offers considerable promise for developing multifunctional micro/nanomotors for a variety of bioassay and biomedical applications.

A CORM loaded nanoplatform for single NIR light-activated bioimaging, gas therapy, and photothermal therapy in vitro.

Carbon monoxide (CO) can cause mitochondrial dysfunction, inducing apoptosis of cancer cells, which sheds light on a potential alternative for cancer treatment. However, the existing CO-based compounds are inherently limited by their chemical nature, such as high biological toxicity and uncontrolled CO release. Therefore, a nanoplatform - UmPF - that addresses such pain points is urgently in demand. In this study, we have proposed a nanoplatform irradiated by near-infrared (NIR) light to release CO. Iron pentacarbonyl (Fe(CO)5) was loaded in the mesoporous polydopamine layer that was coated on rare-earth upconverting nanoparticles (UCNPs). The absorption wavelength of Fe(CO)5 overlaps with the emission bands of the UCNPs in the UV-visible light range, and therefore the emissions from the UCNPs can be used to incite Fe(CO)5 to control the release of CO. Besides, the catechol groups, which are abundant in the polydopamine structure, serve as an ideal locating spot to chelate with Fe(CO)5; in the meantime, the mesoporous structure of the polydopamine layer improves the loading efficiency of Fe(CO)5 and reduces its biological toxicity. The photothermal effect (PTT) of the polydopamine layer is highly controllable by adjusting the external laser intensity, irradiation time and the thickness of the polydopamine layer. The results illustrate that the combination of CO gas therapy (GT) and polydopamine PTT brought by the final nanoplatform can be synergistic in killing cancer cells in vitro. More importantly, the possible toxic side effects can be effectively prevented from affecting the organism, since CO will not be released in this system without near-infrared light radiation.

Laser-induced breakdown spectroscopy as a readout method for immunocytochemistry with upconversion nanoparticles.

Immunohistochemistry (IHC) and immunocytochemistry (ICC) are widely used to identify cancerous cells within tissues and cell cultures. Even though the optical microscopy evaluation is considered the gold standard, the limited range of useful labels and narrow multiplexing capabilities create an imminent need for alternative readout techniques. Laser-induced breakdown spectroscopy (LIBS) enables large-scale multi-elemental analysis of the surface of biological samples, e.g., thin section or cell pellet. It is, therefore, a potential alternative for IHC and ICC readout of various labels or tags (Tag-LIBS approach). Here, we introduce Tag-LIBS as a method for the specific determination of HER2 biomarker. The cell pellets were labeled with streptavidin-conjugated upconversion nanoparticles (UCNP) through a primary anti-HER2 antibody and a biotinylated secondary antibody. The LIBS scanning enabled detecting the characteristic elemental signature of yttrium as a principal constituent of UCNP, thus indirectly providing a reliable way to differentiate between HER2-positive BT-474 cells and HER2-negative MDA-MB-231 cells. The comparison of results with upconversion optical microscopy and luminescence intensity scanning confirmed that LIBS is a promising alternative for the IHC and ICC readout.

Selective Decoating-Induced Activation of Supramolecularly Coated Toxic Nanoparticles for Multiple Applications.

In spite of the rapid emergence of numerous nanoparticles (NPs) for biomedical applications, it is often challenging to precisely control, or effectively tame, the bioactivity/toxicity of NPs, thereby exhibiting limited applications in biomedical areas. Herein, we report the construction of hyaluronic acid (HA)-laminated, otherwise toxic methylviologen (MV), NPs via ternary host-guest complexation among cucurbit[8]uril, trans-azobenzene-conjugated HA, and MV-functionalized polylactic acid NPs (MV-NPs). The high, nonspecific toxicity of MV-NPs was effectively shielded (turned off) by HA lamination, as demonstrated in cells, zebrafish, and mouse models. The supramolecular host-guest interaction-mediated HA coating offered several HA-MV-NP modalities, including hyaluronidase locally and photoirradiation remotely, to precisely remove HA lamination on demand, thereby endowing materials with the capability of selective decoating-induced activation (DIA) for applications as a user-friendly herbicide, a selective antibacterial agent, or an anticancer nanomedicine. This work offers facile supramolecular coating and DIA strategies to effectively tame and precisely control the bioactivity and toxicity of functional nanomaterials for diverse applications.

NIR-Driven Water Splitting H2 Production Nanoplatform for H2-Mediated Cascade-Amplifying Synergetic Cancer Therapy.

As a newly emerging treatment strategy for many diseases, hydrogen therapy has attracted a lot of attention because of its excellent biosafety. However, the high diffusivity and low solubility of hydrogen make it difficult to accumulate in local lesions. Herein, we develop a H2 self-generation nanoplatform by in situ water splitting driven by near-infrared (NIR) laser. In this work, core-shell nanoparticles (CSNPs) of NaGdF4:Yb,Tm/g-C3N4/Cu3P (UCC) nanocomposites as core encapsulated with zeolitic imidazolate framework-8 (ZIF-8) modified with folic acid as shell are designed and synthesized. Due to the acid-responsive ZIF-8 shell, enhanced permeability and retention (EPR) effect, and folate receptor-mediated endocytosis, CSNPs are selectively captured by tumor cells. Upon 980 nm laser irradiation, CSNPs exhibit a high production capacity of H2 and active oxygen species (ROS), as well as an appropriate photothermal conversion temperature. Furthermore, rising temperature increases the Fenton reaction rate of Cu(I) with H2O2 and strengthens the curative effect of chemodynamic therapy (CDT). The excess glutathione (GSH) in tumor microenvironment (TME) can deplete positive holes produced in the valence band of g-C3N4 in the g-C3N4/Cu3P Z-scheme heterojunction. GSH also can reduce Cu(II) to Cu(I), ensuring a continuous Fenton reaction. Thus, a NIR-driven H2 production nanoplatform is constructed for H2-mediated cascade-amplifying multimodal synergetic therapy.

Poly(selenoviologen)-Assembled Upconversion Nanoparticles for Low-Power Single-NIR Light-Triggered Synergistic Photodynamic and Photothermal Antibacterial Therapy.

The development of a highly effective photosensitizer (PS) that can be activated with a low-power single light is a pressing issue. Herein, we report a PS for synergistic photodynamic and photothermal therapy constructed through self-assembly of poly(selenoviologen) on the surface of core-shell NaYF4:Yb/Tm@NaYF4 upconversion nanoparticles. The hybrid UCNPs/PSeV PS showed strong ROS generation ability and high photothermal conversion efficiency (∼52.5%) under the mildest reported-to-date irradiation conditions (λ = 980 nm, 150 mW/cm2, 4 min), leading to a high efficiency in killing methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo. Remarkably, after intravenous injection, the reported PS accumulated preferentially in deep MRSA-infected tissues and achieved an excellent therapeutic index. This PS design realizes a low-power single-NIR light-triggered synergistic phototherapy and provides a simple and versatile strategy to develop safe clinically translatable agents for efficient treatment of deep tissue bacterial inflammations.

A single-particle enumeration method for the detection of Fe2+ based on a near-infrared core-shell upconversion nanoparticle and IR-808 dye composite nanoprobe.

Ferrous ion (Fe2+) is an important component of hemoglobin and plays a role in transporting O2 to human tissues. If iron deficiency is present, iron deficiency anemia may occur, so it is critical to develop sensitive and accurate methods to detect Fe2+. Herein, a novel luminescence energy transfer (ET) system has been designed for the sensitive detection of Fe2+ by a single-particle enumeration (SPE) method in the near-infrared (NIR) region through combining NIR-to-NIR ß-NaGdF4:Yb,Tm@NaYF4 upconversion nanoparticles (UCNPs) and IR-808 dye. IR-808 dye can quench the luminescence of the UCNPs because of the efficient overlap between the absorption spectrum of IR-808 and the emission spectrum of the UCNPs. When Fe2+ and H2O2 are added to the system, the Fenton reaction produces hydroxyl radicals (˙OH). The generated ˙OH reacts with IR-808 and the structure of IR-808 is destroyed. As a result, the ET process is suppressed, causing recovery of the luminescence of the UCNPs, which is reflected as an increase in the number of luminescent particles. Accurate quantification of Fe2+ is achieved by statistically counting the target concentration-dependent luminescent particles. Under the optimal conditions, the linear detection range of Fe2+ is 5-10 000 nM, which is much wider than the ensemble luminescence spectra measurements in bulk solution. Moreover, this strategy can be applied to detection in serum samples with satisfactory results.

Photochemical Ligation to Ultrasensitive DNA Detection with Upconverting Nanoparticles.

In this work, we explore a photochemical ligation reaction to covalently modify oligonucleotide-conjugated upconverting nanoparticles (UCNPs) in the presence of a specific target DNA sequence. The target sequence acts as a hybridization template, bringing together a biotinylated photoactivatable oligonucleotide probe and the oligonucleotide probe that is attached to UCNPs. The illumination of the UCNPs by NIR light to generate UV emission internally or illuminating the photoactivatable probe directly by an external UV light promotes the photochemical ligation reaction, yielding covalently biotin functionalized UCNPs that can be selectively captured in streptavidin-coated microwells. Following this strategy, we developed a DNA sensor with a limit of detection of 1 × 10-18 mol per well (20 fM). In addition, we demonstrate the possibility to create UCNP patterns on the surface of solid supports upon NIR illumination that are selectively formed under the presence of the target oligonucleotide.

Near-Infrared-to-Ultraviolet Light-Mediated Photoelectrochemical Aptasensing Platform for Cancer Biomarker Based on Core-Shell NaYF4:Yb,Tm@TiO2 Upconversion Microrods.

Titanium dioxide (TiO2; as a potential photosensitizer) has good photocurrent performance and chemical stability but often exhibits low utilization efficiency under ultraviolet (UV) region excitation. Herein, we devised a near-infrared light-to-UV light-mediated photoelectrochemical (PEC) aptasensing platform for the sensitive detection of carcinoembryonic antigen (CEA) based on core-shell NaYF4:Yb,Tm@TiO2 upconversion microrods by coupling with target-triggered rolling circle amplification (RCA). The upconversion microrods synthesized through the hydrothermal reaction could act as a photosensing platform to convert the near-infrared (near-IR) excitation into UV emission for generation of photoinduced electrons. The target analyte was determined on a functional magnetic bead by using the corresponding aptamers with a sandwich-type assay format. Upon target CEA introduction, a complex was first formed between capture aptamer-1-conjugated magnetic bead (Apt1-MB) and aptamer-2-primer DNA (Apt2-pDNA). Thereafter, the carried primer DNA by the aptamer-2 paired with linear padlock DNA to trigger the RCA reaction. The guanine (G)-rich product by RCA reaction was cleaved by exonuclease I and exonuclease III (Exos I/III), thereby resulting in the formation of numerous individual guanine bases to enhance the photocurrent of core-shell NaYF4:Yb,Tm@TiO2 upconversion microrods under near-IR illumination (980 nm). Under optimal conditions, the near-IR light-mediated PEC aptasensing system could exhibit good photoelectrochemical response toward target CEA and allowed for the detection of target CEA as low as 3.6 pg mL-1. High reproducibility and good accuracy were achieved for analysis of human serum specimens. Importantly, the near-IR-activated PEC aptasensing scheme provides a promising platform for ultrasensitive detection of other biomolecules.

Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by using lanthanide-doped upconversion nanoparticles.

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.

152 W average power Tm-doped fiber CPA system.

A high-power thulium (Tm)-doped fiber chirped-pulse amplification system emitting a record compressed average output power of 152 W and 4 MW peak power is demonstrated. This result is enabled by utilizing Tm-doped photonic crystal fibers with mode-field diameters of 35 µm, which mitigate detrimental nonlinearities, exhibit slope efficiencies of more than 50%, and allow for reaching a pump-power-limited average output power of 241 W. The high-compression efficiency has been achieved by using multilayer dielectric gratings with diffraction efficiencies higher than 98%.

Activation cross-sections of proton induced nuclear reactions on thulium in the 20-45 MeV energy range.

Cross-sections of proton induced nuclear reactions on (169)Tm were measured in the 20-45MeV energy range using the standard stacked-foil irradiation technique and high resolution gamma-ray spectroscopy. Experimental cross-sections and derived integral yields are reported for the production of (169,167,166)Yb and (168,167,166)Tm radioisotopes. The experimental data are analysed and compared to results of the earlier measurements and the theoretical model codes ALICE-IPPE, EMPIRE and TALYS. Application of the new cross-sections to the production of the (167)Tm medical radioisotope is discussed.

Broadband near-infrared emission in Tm3+-Dy3+ codoped amorphous chalcohalide films fabricated by pulsed laser deposition.

Structural and near-infrared (NIR) emission properties were investigated in the Tm(3+)-Dy(3+) codoped Ge-Ga-based amorphous chalcohalide films fabricated by pulsed laser deposition. The homogeneous films illustrated similar random network to the glass target according to the measurements of X-ray diffraction, X-ray photoelectron spectroscopy, and Raman spectroscopy. An 808 nm laser diode pumping generated a superbroadband NIR emission ranging from 1050 to 1570 nm and the other intense broadband NIR emission centered at ~1800 nm, which was attributed to the efficient energy transfer from Tm(3+) to Dy(3+) ions. This was further verified by the broad-range excitation measurements near the Urbach optical-absorption edge involved defect states. The results shed light on the potential highly integrated planar optical device applications of the codoped amorphous chalcohalide films.

Experimental study of the excitation functions of proton induced nuclear reactions on (167)Er for production of medically relevant (167)Tm.

(167)Tm (T(1/2)=9.25d) is a candidate radioisotope for medical therapy and diagnostics due to its Auger-electron and low-energy X- and gamma-ray emission. Excitation functions of the (167)Er(p,n)(167)Tm reaction and (168)Er(p,n)(168)Tm, (167)Er(p,2n)(166)Tm, (166)Er(p,2n)(165)Tm disturbing reactions were measured up to 15MeV by using the stacked foil irradiation technique and gamma-ray spectroscopy. The measured excitation functions agree well with the results of ALICE-IPPE, EMPIRE-II and TALYS nuclear reaction model codes. The thick target yield of (167)Tm in the 15-8MeV energy range is 6.9MBq/microAh. A short comparison of charged particle production routes of (167)Tm is given.

Near-infrared luminescence of Nd3+ and Tm3+ ions doped ZnO nanocrystals.

Intense near-infrared luminescence of Nd(3+) and Tm(3+) ions in the region of 860-1550 nm were achieved in 10-15 nm wurtzite ZnO nanocrystals fabricated by a facile sol-gel process. The optical properties of Nd(3+) and Tm(3+) ions were investigated by using the steady-state and time-resolved laser spectroscopy. Due to the well-ordered crystal-field surroundings experienced by Nd(3+) and Tm(3+) ions, sharp and well resolved emission lines of Nd(3+) and Tm(3+) ions were identified at 4-300 K. Time-resolved luminescence and decay behaviors of the (4)F(3/2)-->(4)I(11/2) transition of Nd(3+) ions reveal the existence of multiple Nd(3+) sites in ZnO nanocrystals.

[The use of CaF2:Tm-dosimetry in pion and heavy ion fields]. / Anwendung von CaF2:Tm-Dosimetrie in Pionen- und Schwerionenfeldern.

Under High-LET-irradiation the efficiency of the main glow peaks of CaF2:Tm varies strongly with LET. This leads to a simple Two-Component-dosimeter, that allows to measure dose and average LET simultaneously.

[Digital recording of glow curves of the TLD-300 thermoluminescent dosimetry detector by adaptation of a sum of Gauss function to the measured values]. / Digitale Erfassung der Glowkurven von TLD-300-Detektoren und Datenreduktion durch Anpassung einer Summe von Gaussfunktionen an die Messwerte.

Calciumfluoride doped with Thulium (TLD-300) can be used to measure simultaneously with one detector neutron and photon absorbed dose in mixed neutron-photon beams. The accuracy in dose measurements can be increased by use of a computer. Additionally the number of data needed to store a glow curve can be reduced from 240 to 24 by fitting a sum of Gauss functions to the measured glow curve.