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In this work we adapt rare-earth-ion-doped NaYF 4 nanoparticles coated with a silicon oxide shell (NaYF 4 :20%Yb,0.2%Tm@SiO 2 ) for biological and medical applications (for example, imaging of cancer cells and therapy at the nano level). The wide upconversion emission range under 980 nm excitation allows one to use the nanoparticles for cancer cell (4T1) photodynamic therapy (PDT) without a photosensitizer. The reactive oxygen species (ROS) are generated by Tm/Yb ion upconversion emission (blue and UV light). The in vitro PDT was tested on 4T1 cells incubated with NaYF 4 :20%Yb,0.2%Tm@SiO 2 nanoparticles and irradiated with NIR light. After 24 h, cell viability decreased to below 10%, demonstrating very good treatment efficiency. High modification susceptibility of the SiO 2 shell allows for attachment of biological molecules (specific antibodies). In this work we attached the anti-human IgG antibody to silane-PEG-NHS-modified NaYF 4 :20%Yb,0.2%Tm@SiO 2 nanoparticles and a specifically marked membrane model by bio-conjugation. Thus, it was possible to perform a selective search (a high-quality optical method with a very low-level organic background) and eventually damage the targeted cancer cells. The study focuses on therapeutic properties of NaYF 4 :20%Yb,0.2%Tm@SiO 2 nanoparticles and demonstrates, upon biological functionalization, their potential for targeted therapy., (Creative Commons Attribution license.)

Radiopharmaceuticals with therapeutic applications are designed to deliver high doses of radiation to target organs with minimizing unwanted radiation to healthy tissues. Owing to the potential of targeted radiotherapy to treat a wide range of malignancies, 170 Tm -EDTMP was developed for possible therapeutic applications. This study describes absorbed dose prediction of 170 Tm-EDTMP in human organs after animal injection which is determined via medical internal radiation dose (MIRD) and MCNP-4C code methods. It was estimated that a 1-MBq administration of 170 Tm-EDTMP into the human body would result in an absorbed dose of 37.9 mGy (MIRD method) and 38.02 mGy (MCNP-4C code) in the bone surface after 60 days post injection. Highest and lowest difference between MIRD and MCNP results are for lung and bone surface respectively. Finally, the results show that there is a good agreement between MIRD method and MCNP-4C simulation code for absorbed dose estimation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rare-earth upconversion nanoparticles (UCNPs) are considered stable nanoprobes with low toxicity and deep tissue penetration. However, the increasing use of UCNPs has raised concerns about their potential toxicity in living organisms. Very few studies have reported the toxicity of UCNPs; hence, it is not possible to conclude yet that UCNPs are safe. In this study, the distribution of PEGylated NaYF 4 :Yb/Tm/Gd nanoparticles (PEG-UCNPs) in female Balb/c mice following intravenous administration, and imaging in the spleen, liver and kidney was examined by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). PEG-UCNPs distributed primarily to the liver and spleen, with significant but lower levels being noted in the kidneys, heart, and lungs. At the sub-organ level, PEG-UCNPs mainly accumulated within the red pulp of the spleen instead of the white pulp, which indicated that PEG-UCNPs are poorly immunogenic, or not immunogenic at all. The imaging of Cu in the liver and spleen showed that the primary clearance organ for PEG-UCNPs is the liver, although they are accumulated in the spleen rather than the liver. This can be explained by the fact that excess superoxide anions produced by phagocytosis of the PEG-UCNPs need Cu-Zn-superoxide dismutase to be converted to hydrogen peroxide. From the Fe, Cu, and Zn imaging of the kidney, it was concluded that PEG-UCNPs do not exhibit nephrotoxicity.

The objective of the present work is to formulate 170 Tm-EDTMP using an in-house freeze-dried EDTMP kit and evaluate its potential as a bone pain palliation agent. Patient dose of 170 Tm-EDTMP was prepared with high radiochemical purity using the lyophilized kit at room temperature within 15min. Pre-clinical evaluation in normal Wistar rats revealed selective skeletal accumulation with extended retention. Preliminary clinical investigation in 8 patients with disseminated skeletal metastases exhibited selective uptake in the bone and retention therein for a long duration., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The combination therapy has exhibited important potential for the treatment of cancers, especially for drug-resistant cancers. In this report, bi-functional nanoprobes based on doxorubicin (DOX)-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers (FA-NPs-DOX) were synthesized for in vivo near infrared (NIR)-triggered inorganic photodynamic therapy (PDT) and enhanced chemotherapy to overcome the multidrug resistance (MDR) in breast cancers. Using the up-conversion luminescence (UCL) performance of NaYF4:Yb/Tm converting near-infrared (NIR) into ultraviolent (UV) lights, reactive oxygen species (ROS) were triggered from TiO2 inorganic photosensitizers for PDT under the irradiation of a 980 nm laser, by which the deep-penetration and low photo-damage could be reached. Moreover, nanocarrier delivery and folic acid (FA) targeting promoted the cellular uptake, and accelerated the release of DOX in drug-sensitive MCF-7 and resistant MCF-7/ADR cells. The toxicity assessment in vitro and in vivo revealed the good biocompatibility of the as-prepared FA-NPs-DOX nanocomposites. By the combination of enhanced chemotherapy and NIR-triggered inorganic PDT, the viability of MCF-7/ADR cells could decrease by 53.5%, and the inhibition rate of MCF-7/ADR tumors could increase up to 90.33%, compared with free DOX. Therefore, the MDR of breast cancers could be obviously overcome by enhanced chemotherapy and NIR-triggered inorganic PDT of FA-NPs-DOX nanocomposites under the excitation of a 980 nm laser., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Due to the fact that cellular therapies are increasingly finding application in clinical trials and promise success by treatment of fatal diseases, monitoring strategies to investigate the delivery of the therapeutic cells to the target organs are getting more and more into the focus of modern in vivo imaging methods. In order to monitor the distribution of the respective cells, they can be labeled with lanthanide complexes such as thulium-1,4,7,10-tetraazacyclodoecane-α,α,α,α-tetramethyl-1,4,7,10-tetraacetic acid (Tm(DOTMA)). In this study, experiments on a mouse model with two different cell types, namely, tumor cells and macrophages labeled with Tm(DOTMA), were performed. The systemic distribution of Tm(DOTMA) of both cell types was investigated by means of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS). Using the high resolution of 25 μm, distribution maps of Tm in different tissues such as tumor, liver, lung, and spleen as well as in explanted gel pellets were generated and the behavior of the labeled cells inside the tissue was investigated. Additionally, quantitative data were obtained using homemade matrix-matched standards based on egg yolk. Using this approach, limits of detection and quantification of 2.2 and 7.4 ng·g(-1), respectively, and an excellent linearity over the concentration range from 0.01 to 46 μg·g(-1) was achieved. The highest concentration of the label agent, 32.4 μg·g(-1), in tumor tissue was observed in the area of the injection of the labeled tumor cells. Regarding the second experiment with macrophages for cell tracking, Tm was detected in the explanted biogell pellet with relatively low concentrations below 60 ng·g(-1) and in the liver with a relatively high concentration of 10 μg·g(-1). Besides thulium, aluminum was detected with equal distribution behavior in the tumor section due to a contamination resulting from the labeling procedure, which includes the usage of an Al electrode.