Designing photon upconversion nanoparticles capable of intense emission in whole human blood.

The properties of upconverting nanoparticles (UCNPs) are crucial for their applications in biomedicine. For studies of organisms and biological materials, the penetration depth of excitation light is also essential as the depth from which the luminescence can be detected. Currently, many researchers are trying to obtain UCNPs with intense emission under excitation wavelengths from the biological transparency windows to increase the penetration depth. However, studies comparing the properties of various types of UCNPs in real conditions are rare. This article shows how deep the 808, 975, 1208, and 1532 nm laser radiation penetrates human blood. Moreover, we determined how thick a layer of blood still permits for observation of the luminescence signal. The measured luminescence properties indicated that the near-infrared light could pass through the blood even to a depth of 7.5 mm. The determined properties of core/shell NaErF4/NaYF4 materials are the most advantageous, and their emission is detectable through 3.0 mm of blood layer using a 1532 nm laser. We prove that the NaErF4/NaYF4 UCNPs can be perfect alternatives for the most studied NaYF4:Yb3+,Er3+/NaYF4. Additionally, the setup proposed in this article can potentially decrease reliance on animal testing in initial biomedicine research.

Bright photon upconversion in LiYbF4:Tm3+@LiYF4 nanoparticles and their application for singlet oxygen generation and in immunoassay for SARS-CoV-2 nucleoprotein.

Photon upconversion is an intensively investigated phenomenon in the materials sciences due to its unique applications, mainly in biomedicine for disease prevention and treatment. This study reports the synthesis and properties of tetragonal LiYbF4:Tm3+@LiYF4 core@shell nanoparticles (NPs) and their applications. The NPs had sizes ranging from 18.5 to 23.7 nm. As a result of the energy transfer between Yb3+ and Tm3+ ions, the synthesized NPs show intense emission in the ultraviolet (UV) range up to 347 nm under 975 nm excitation. The bright emission in the UV range allows for singlet oxygen generation in the presence of hematoporphyrin on the surface of NPs. Our studies show that irradiation with a 975 nm laser of the functionalized NPs allows for the production of amounts of singlet oxygen easily detectable by Singlet Oxygen Sensor Green. The high emission intensity of NPs at 800 nm allowed the application of the synthesized NPs in an upconversion-linked immunosorbent assay (ULISA) for highly sensitive detection of the nucleoprotein from SARS-CoV-2, the causative agent of Covid-19. This article proves that LiYbF4:Tm3+@LiYF4 core@shell nanoparticles can be perfect alternatives for the most commonly studied upconverting NPs based on the NaYF4 host compound and are good candidates for biomedical applications.

Ecotoxicity of non- and PEG-modified lanthanide-doped nanoparticles in aquatic organisms.

Various types of nanoparticles (NPs) have been widely investigated recently and applied in areas such as industry, the energy sector, and medicine, presenting the risk of their release into the environment. The ecotoxicity of NPs depends on several factors such as their shape and surface chemistry. Polyethylene glycol (PEG) is one of the most often used compounds for functionalisation of NP surfaces, and its presence on the surfaces of NPs may affect their ecotoxicity. Therefore, the present study aimed to assess the influence of PEG modification on the toxicity of NPs. As biological model, we chose freshwater microalgae, a macrophyte and invertebrates, which to a considerable extent enable the assessment of the harmfulness of NPs to freshwater biota. SrF2:Yb3+,Er3+ NPs were used to represent the broad group of up-converting NPs, which have been intensively investigated for medical applications. We quantified the effects of the NPs on five freshwater species representing three trophic levels: the green microalgae Raphidocelis subcapitata and Chlorella vulgaris, the macrophyte Lemna minor, the cladoceran Daphnia magna and the cnidarian Hydra viridissima. Overall, H. viridissima was the most sensitive species to NPs, which affected its survival and feeding rate. In this case, PEG-modified NPs were slightly more toxic than bare ones (non-significant results). No effects were observed on the other species exposed to the two NPs at the tested concentrations. The tested NPs were successfully imaged in the body of D. magna using confocal microscopy; both NPs were detected in the D. magna gut. The results obtained reveal that SrF2:Yb3+,Er3+ NPs can be toxic to some aquatic species; however, the structures have low toxicity effects for most of the tested species.

Digital and Analog Detection of SARS-CoV-2 Nucleocapsid Protein via an Upconversion-Linked Immunosorbent Assay.

The COVID-19 crisis requires fast and highly sensitive tests for the early stage detection of the SARS-CoV-2 virus. For detecting the nucleocapsid protein (N protein), the most abundant viral antigen, we have employed upconversion nanoparticles that emit short-wavelength light under near-infrared excitation (976 nm). The anti-Stokes emission avoids autofluorescence and light scattering and thus enables measurements without optical background interference. The sandwich upconversion-linked immunosorbent assay (ULISA) can be operated both in a conventional analog mode and in a digital mode based on counting individual immune complexes. We have investigated how different antibody combinations affect the detection of the wildtype N protein and the detection of SARS-CoV-2 (alpha variant) in lysed culture fluid via the N protein. The ULISA yielded a limit of detection (LOD) of 1.3 pg/mL (27 fM) for N protein detection independent of the analog or digital readout, which is approximately 3 orders of magnitude more sensitive than conventional enzyme-linked immunosorbent assays or commercial lateral flow assays for home testing. In the case of SARS-CoV-2, the digital ULISA additionally improved the LOD by a factor of 10 compared to the analog readout.

Influence of the synthesis route on the spectroscopic, cytotoxic, and temperature-sensing properties of oleate-capped and ligand-free core/shell nanoparticles.

The right choice of synthesis route for upconverting nanoparticles (UCNPs) is crucial for obtaining a well-defined product with a specific application capability. Thus we decided to compare the physicochemical, cytotoxic, and temperature-sensing properties of UCNPs obtained from different rare earth (RE) ions, which has been made for the first time in a single study. The core/shell NaYF4:Yb3+,Er3+/NaYF4 UCNPs were obtained by reaction in a mixture of oleic acid and octadecene, and their highly stable water colloids were prepared using the ligand-free modification method. Both oleate-capped and ligand-free UCNPs exhibited a bright upconversion emission upon 975 nm excitation. Moreover, slope values, emission quantum yields, and luminescence lifetimes confirmed an effective energy transfer between the Yb3+ and Er3+ ions. Additionally, the water colloids of the UCNPs showed temperature-sensing properties with a good thermal sensitivity level, higher than 1 % K-1 at 358 K. Evaluation of the cytotoxicity profiles of the obtained products indicated that cell viability was decreased in a dose-dependent manner in the analyzed concentration range.

Improvement of ligand-free modification strategy to obtain water-stable up-converting nanoparticles with bright emission and high reaction yield.

Water-dispersible up-converting nanoparticles (UCNPs) are known to be very effective in biomedical applications. Research groups have paid special attention to the synthesis of hydrophilic UCNPs with good physicochemical properties. Being aware of this, we decided to improve the ligand-free modification method of OA-capped NaYF4:Yb3+,Er3+/NaYF4 UCNPs prepared by precipitation in high-boiling-point solvents as the thus-far reported methods do not provide satisfactory results. Different molarities of hydrochloric acid and various mixing times were selected to remove the organic ligand from the NPs' surface and to discover the most promising modification approach. Highly water-stable colloids were obtained with a very high reaction yield of up to 96%. Moreover, the acid treatment did not affect the morphology and the size of the product. All of the crystals exhibited a bright up-conversion emission under 975-nm excitation, which confirmed the two-photon excitation and effective energy transfer between the used dopant ions. Thus, we could establish the most successful ligand-free modification procedure.