Effect of the dose on the toxicokinetics of a quaternary mixture of rare earth elements administered to rats.

Large human biomonitoring studies are starting to assess exposure to rare earth elements (REEs). Yet, there is a paucity of data on the toxicokinetics of these substances to help interpret biomonitoring data. The objective of the study was to document the effect of the administered dose on the toxicokinetics of REEs. Male Sprague-Dawley rats were injected intravenously with 0.3, 1 or 10 mg/kg body weight (bw) of praseodynium chloride (PrCl3), cerium chloride (CeCl3), neodymium chloride (NdCl3) and yttrium chloride (YCl3) administered together as a mixture. Serial blood samples were withdrawn up to 72 h following injection, and urine and feces were collected at predefined time intervals up to 7 days post-dosing. The REEs were measured by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). For a given REE dose, the time courses in blood, urine and feces were similar for all four REEs. However, the REE dose administered significantly impacted their kinetics, as lower cumulative excretion in urine and feces was associated with higher REE doses. The fraction of REE remaining in rat tissues at the terminal necropsy on post-dosing day 7 also increased with the dose administered, most notably in the lungs and spleen at the 10 mg/kg bw dose. The toxicokinetic parameters calculated from the blood concentration-time profiles further showed significant increases in the mean residence time (MRTIV) for all four REEs at the 10 mg/kg bw dose. The shift in the REE kinetics at high dose may be explained by a higher retention in lysosomes, the main organelle responsible for accumulation of these REEs in different tissues.

The ROS-generating photosensitizer-free NaYF4:Yb,Tm@SiO2upconverting nanoparticles for photodynamic therapy application.

In this work we adapt rare-earth-ion-doped NaYF4nanoparticles coated with a silicon oxide shell (NaYF4:20%Yb,0.2%Tm@SiO2) 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). Thein vitroPDT was tested on 4T1 cells incubated with NaYF4:20%Yb,0.2%Tm@SiO2nanoparticles and irradiated with NIR light. After 24 h, cell viability decreased to below 10%, demonstrating very good treatment efficiency. High modification susceptibility of the SiO2shell allows for attachment of biological molecules (specific antibodies). In this work we attached the anti-human IgG antibody to silane-PEG-NHS-modified NaYF4:20%Yb,0.2%Tm@SiO2nanoparticles 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 NaYF4:20%Yb,0.2%Tm@SiO2nanoparticles and demonstrates, upon biological functionalization, their potential for targeted therapy.

A Janus upconverting nanoplatform with biodegradability for glutathione depletion, near-infrared light induced photodynamic therapy and accelerated excretion.

The major limitations of photodynamic therapy (PDT) are the poor tissue penetration of excitation light and the neutralization of reactive oxygen species (ROS) generated by overexpressed glutathione (GSH) in cancer cells. Despite tremendous efforts to design nanoplatforms, PDT still suffers from unsatisfactory effects. Furthermore, the residual of nanomaterials in the body has restricted their clinical application. To address these issues, Janus nanocomposites containing an Yb/Er codoped NaYF4 upconverting nanocrystal head and a disulfide-bridged mesoporous organosilicon body (UCN/MON) with loaded chlorin e6 (Ce6) were designed. On one hand, the upconverting nanocrystal head can convert near-infrared (NIR) light into visible light to activate Ce6 to release ROS. On the other hand, the silica body can be degraded though a redox reaction with GSH, to not only improve the tumor selectivity of the photosensitizer by redox- and pH-triggered Ce6 release, but also diminish the concentration of GSH in cancer cells to reduce the depletion of ROS. Thereby, an enhanced PDT triggered by NIR irradiation was achieved. Furthermore, UCN/MONs showed a higher clearance rate after therapeutic actions than nonbiodegradable UCN/MSNs due to their biocompatibility. Taken together, this work revealed the potential of UCN/MONs for highly efficient and NIR-induced PDT, highlighting the prospects of UCN/MONs in the clinic.

The synergistic effects of SrF2 nanoparticles, YSZ nanoparticles, and poly-ε-l-lysin on physicomechanical, ion release, and antibacterial-cellular behavior of the flowable dental composites.

Resin-based pit-and-fissure sealants (flowable resin composites) were formulated using bisphenol-A-glycerolatedimethacrylate (Bis-GMA)-triethylene glycol dimethacrylate-(TEGDMA)-diurethanedimethacrylate (UDMA) mixed monomers and multiple fillers, including synthetic strontium fluoride (SrF2) nanoparticles as a fluoride-releasing and antibacterial agent, yttria-stabilized zirconia (YSZ) nanoparticles as an auxiliary filler, and poly-ε-l-lysin (ε-PL) as an auxiliary antibacterial agent. Based on the physical, mechanical and initial antibacterial properties, the formulated nano-sealant containing 5 wt% SrF2, 5 wt% YSZ and 0.5 wt% ε-PL was selected as the optimal specimen and examined for ion release and cytotoxicity. The results showed an average release rate of 0.87 µg·cm-2·day-1 in the aqueous medium (pH 6.9) and 1.58 µg·cm-2·day-1 in acidic medium (pH 4.0). The maximum cytotoxicity of 20% toward human bone marrow mesenchymal stem cells (hMSCs) was observed according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) cytotoxicity assay and acridine orange staining test. A synergy between SrF2 nanoparticles and ε-PL exhibited a better antibacterial activity in terms of colony reduction compared to the other samples. However, the inclusion of SrF2 and ε-PL caused mechanically weakening of the sealants that was partly compensated by incorporation of YSZ nanoparticles (up to 10 wt%).

Model-based rationalization of mixture toxicity and accumulation in Triticum aestivum upon concurrent exposure to yttrium, lanthanum, and cerium.

Rare earth elements (REEs) often co-exist in the environment, but predicting their 'cocktail effects' is still challenging, especially for high-order mixtures with more than two components. Here, we systematically investigated the toxicity and accumulation of yttrium, lanthanum, and cerium mixtures in Triticum aestivum following a standardized bioassay. Toxic effects of mixtures were predicted using the reference model of Concentration Addition (CA), Ternary model, and Ternary-Plus model. Interactions between the REEs in binary and ternary mixtures were determined based on external and internal concentrations, and their magnitude estimated from the parameters deviated from CA. Strong antagonistic interactions were found in the ternary mixtures even though there were no significant interactions in the binary mixtures. Predictive ability increased when using the CA model, Ternary model, and Ternary-Plus model, with R2= 0.78, 0.80, and 0.87 based on external exposure concentrations, and R2= 0.72, 0.73, and 0.79, respectively based on internal concentrations. The bioavailability-based model WHAM-FTOX explained more than 88 % and 85 % of the toxicity of binary and ternary REE treatments, respectively. Our result showed that the Ternary-Plus model and WHAM-FTOX model are promising tools to account for the interaction of REEs in mixtures and could be used for their risk assessment.

Scandium, yttrium, and lanthanide contents in soil from Serbia and their accumulation in the mushroom Macrolepiota procera (Scop.) Singer.

The mobility (fractionation) of rare earth elements (REEs) and their possible impacts on ecosystems are still relatively unknown. Soil samples were collected from two sites in central Serbia, an unpolluted mountain region (site 1) and a forest near a city (site 2). In order to investigate REE fractions (acid-soluble/exchangeable, reducible, oxidizable, and residual) in soils, BCR sequential extraction was performed. Additionally, the content of REEs was also determined in stipes and caps of the mushroom Macrolepiota procera, growing in the observed sites. Sc, Y, and lanthanide contents were determined by inductively coupled plasma mass spectrometry (ICP-MS), and results were subjected to multivariate data analysis. Application of pattern recognition technique revealed the existence of two distinguished clusters belonging to different geographical sites and determined by greater levels of Sc, Y, and lanthanides in Goc soil compared to Trstenik soil. Additionally, PCA analysis showed that REEs in soil were concentrated in two groups: the first consisted of elements belonging to light REEs and the second contained heavy REEs. These results suggest that the distribution of REEs in soils could indicate the geographical origin and type of soil. The bioconcentration factors and translocation factors for each REE were also calculated. This study provides baseline data on the rare earth element levels in the wild edible mushroom M. procera, growing in Serbia. In terms of bioconcentration and bioexclusion concept, Sc, Y, and REEs were bioexcluded in M. procera for both studied sites.

Phytotoxicity of individual and binary mixtures of rare earth elements (Y, La, and Ce) in relation to bioavailability.

Rare earth elements (REEs) are typically present as mixtures in the environment, but a quantitative understanding of mixture toxicity and interactions of REEs is still lacking. Here, we examined the toxicity to wheat (Triticum aestivum L.) of Y, La, and Ce when applied individually and in combination. Both concentration addition (CA) and independent action (IA) reference models were used for mixture toxicity analysis because the toxicity mechanisms of REEs remain obscure. Upon single exposure, the EC50s of Y, La, and Ce, expressed as dissolved concentrations, were 1.73 ±â€¯0.24 µM, 2.59 ±â€¯0.23 µM, and 1.50 ±â€¯0.22 µM, respectively. The toxicity measured with relative root elongation followed La < Y ≈ Ce, irrespective of the dose descriptors. The use of CA and IA provided similar estimates of REE mixture interactions and toxicity. When expressed as dissolved metal concentrations, nearly additive effects were observed in Y-La and La-Ce mixtures, while antagonistic interactions were seen in Y-Ce mixtures. When expressed as free metal activities, antagonistic interactions were found for all three binary mixtures. This can be explained by a competitive effect of REEs ions for binding to the active sites of plant roots. The application of a more elaborate MIXTOX model in conjunction with the free ion activities, which incorporates the non-additive interactions and bioavailability-modifying factors, well predicted the mixture toxicity (with >92% of toxicity variations explained). Our results highlighted the importance of considering mixture interactions and subsequent bioavailability in assessing the joint toxicity of REEs.

Y2O3 Nanoparticles Caused Bone Tissue Damage by Breaking the Intracellular Phosphate Balance in Bone Marrow Stromal Cells.

Y2O3 nanoparticles (NPs) have become great promising products for numerous applications in nanoscience especially for biomedical application, therefore increasing the probability of human exposure and gaining wide attention in biosecurity. It is well known that rare earth (RE) materials are deposited in the bone and excreted very slowly. Nevertheless, the effect of Y2O3-based NPs on bone metabolism has not been exactly known yet. In the present study, the effects of Y2O3 NPs on bone marrow stromal cells (BMSCs) and bone metabolism in mice after intravenous injection were studied. The results demonstrated that Y2O3 NPs could be taken up into BMSCs and localized in acidifying intracellular lysosomes and underwent dissolution and transformation from Y2O3 to YPO4, which could lead to a break in the intracellular phosphate balance and induce lysosomal- and mitochondrial-dependent apoptosis pathways. Furthermore, after being administered to mice, a higher concentration of yttrium occurred in bone, which caused the apoptosis of bone cells and induced the destruction of bone structure. However, the formation of a YPO4 coating on the surface of Y2O3 NPs by pretreatment of Y2O3 NPs in lysosome-simulated body fluid could observably decrease the toxicity in vivo and in vitro. This study may be useful for practical application of Y2O3 NPs in the biomedical field.

Luminescent Carrier, Tb3+-Doped Layered Yttrium Hydroxide, for Delivery Systems.

Layered rare-earth hydroxides (LRHs) with high anion exchangeability between the hydroxocation layers, where a large variety of organic anions can be sheltered, are employed to construct hybrid systems that slowly release active organic ingredients. More importantly, it is possible to endow LRHs with a photoluminescence capability by doping activator ions such as Ce3+, Eu3+, and Tb3+ into matrices. In the present work, we explored Tb3+-doped layered yttrium hydroxide Y1.80Tb0.20(OH)5Cl· nH2O (LYH:Tb) nanosheets as a luminescent carrier for sustained release of salicylic acid (2-hydroxybenzoic acid), an example of nonsteroidal anti-inflammatory drugs and antimicrobial agents. Salicylate (sal) was intercalated into the interlayer gallery of LYH:Tb via a direct ion-exchange reaction. An observed variation in basal spacing suggested that salicylate anions are arranged in an interdigitated bilayer manner in the interlayer space of LYH:Tb. As generally observed in organic/inorganic hybrid systems, the thermal and photostabilities of salicylate were significantly improved after intercalation compared to its free state. The release kinetics of salicylate from sal-LYH:Tb hybrids in a saline solution at pH = 7.4 showed a highly sustained release of salicylate. Among various examined mathematical models, the parabolic diffusion equation best described the cumulative salicylate release. In particular, the salicylate intercalation led to the characteristic 5D4 → 7F J ( J = 6, 5, and 4) green emission of Tb3+ by its sensitization followed by the energy transfer to sal-LYH:Tb, whereas typical blue emission of salicylate was recovered after its release from the interlayer gallery of the LYH:Tb carrier. This green/blue luminescence change behavior provides a useful technique for in situ monitoring of the delivery and release of salicylate at target sites. The sal-LYH:Tb hybrid, with antimicrobial properties, was readily dispersed into a biodegradable polymer, polyvinyl alcohol, to prepare a transparent, UV-shielding, and luminescent composite that is applicable as an antimicrobial polymer to retard or prevent microbial growth.

Elemental bio-imaging of PEGylated NaYF4:Yb/Tm/Gd upconversion nanoparticles in mice by laser ablation inductively coupled plasma mass spectrometry to study toxic side effects on the spleen, liver and kidneys.

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 NaYF4: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.

Kinetics-mediate fabrication of multi-model bioimaging lanthanide nanoplates with controllable surface roughness for blood brain barrier transportation.

Effective delivery of imaging agents or therapeutics to the brain has remained elusive due to the poor blood-brain barrier (BBB) permeability, resulting in the apparent risks of inefficient diagnosis and therapeutic agents for brain disease. Herein, we report on the surface roughness mediated BBB transportation for the first time. The lanthanide-based core/shell/shell structured NaYF4:Yb,Er@NaGdF4:Yb@NaNdF4:Yb nanoplates with controllable surface roughness and multi-model bioimaging features were synthesized and used to evaluate the surface roughness dependent BBB permeability without any surface bio-functionalization. By controlling the kinetics of the shell coating process, the hexagon-disc, multi-petals and six-petals nanoplates with different surface roughness can be obtained. Comparing with the NPs with less Ra and receptor-conjugated NPs, the obtained six-petals nanoplates with highest roughness exhibit excellent performance in BBB transportation and tumor targeting, which lay solid foundation for the diagnosis and the therapy of brain tumor.

Assessment of genotoxicity and biodistribution of nano- and micron-sized yttrium oxide in rats after acute oral treatment.

The increasing use of yttrium oxide (Y2 O3 ) nanoparticles (NPs) entails an improved understanding of their potential impact on the environmental and human health. In the present study, the acute oral toxicity of Y2 O3 NPs and their microparticles (MPs) was carried out in female albino Wistar rats with 250, 500 and 1000 mg kg-1 body weight doses. Before the genotoxicity evaluation, characterization of the particles by transmission electron microscopy, dynamic light scattering and laser Doppler velocimetry was performed. The genotoxicity studies were conducted using micronucleus and comet assays. Results showed that Y2 O3 NP-induced significant DNA damage at higher dose (1000 mg kg-1 body weight) in peripheral blood leukocytes and liver cells, micronucleus formation in bone marrow and peripheral blood cells. The findings from biochemical assays depicted significant alterations in aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, superoxide dismutase, reduced glutathione, catalase and lactate dehydrogenase levels in serum, liver and kidneys at the higher dose only. Furthermore, tissue biodistribution of both particles was analyzed by inductively coupled plasma optical emission spectrometry. Bioaccumulation of yttrium (Y) in all tissues was significant and dose-, time- and organ-dependent. Moreover, Y2 O3 NP-treated rats exhibited higher tissue distribution along with greater clearance through urine whereas Y2 O3 MP-dosed animals depicted the maximum amount of Y in the feces. Hence, the results indicated that bioaccumulation of Y2 O3 NPs via its Y ions may induce genotoxic effects.

Biokinetics of yttrium and comparison with its geochemical twin holmium.

The transition metal yttrium (Y, atomic number 39) is chemically similar to elements in the lanthanide family (atomic numbers 57-71) and is found with the lanthanides in rare earth ores. Yttrium and the lanthanide holmium are referred to as geochemical twins because they generally show little fractionation from metamorphic or weathering processes, due to their closely similar chemical properties and nearly identical ionic radii. Extensive measurements on rocks, soils, and meteorites indicate that the Y/Ho mass concentration ratio rarely falls far from the so-called chondritic or solar system ratio of ∼26. This paper presents a new biokinetic model for yttrium in adult humans and examines whether yttrium and holmium may be biological as well as geochemical twins, considering model-based comparisons of their systemic behaviours in adult humans and model-free comparisons of their concentration ratios in human tissues and various types of vegetation. It appears that yttrium and holmium behave similarly in the human body and that their concentration ratios tend to cluster near the chondritic value in human tissues as well as plants, but the comparative information is too limited and imprecise to determine whether they are extremely close biological analogues.

Biodistribution, excretion, and toxicity of polyethyleneimine modified NaYF4:Yb,Er upconversion nanoparticles in mice via different administration routes.

Upconversion nanoparticles (UCNPs) have drawn much attention in biomedicine, and the clinical translation of UCNPs is closely related to their toxicity and metabolism in vivo. In this study, we chose polyethyleneimine modified NaYF4:Yb,Er upconversion nanoparticles (abbreviated as PEI@UCNPs) to systematically study the biodistribution in mice using intravenous (i.v.), intraperitoneal (i.p.), and intragastric (i.g.) administration. The i.p. injected PEI@UCNPs exhibited obvious accumulation in the spleen within 30 days. Comparably, PEI@UCNPs via i.g. administration exhibited an accumulation that decreased with time in various body tissues and were found mainly in the ileum and cecum but were rather low in concentration in the other examined organs. For the i.v. injected group, the UCNPs exhibited an obvious clearance from the body within 30 days and the accumulation in the spleen gradually decreased. Furthermore, 64Cu labeled PEI@UCNPs were i.v. injected for real-time photon emission computed tomography (PET) imaging to further confirm the biodistribution in mice. Afterward, the excretion routes of the PEI@UCNPs were evaluated. For i.p. injected groups, the UCNPs were slowly and partly excreted via feces and urine for 30 days, and a large number of the UCNPs were steadily excreted via feces for the i.v. group, suggesting that the UCNPs via i.v. injection can be potentially used for imaging and therapy studies in vivo. However, for the i.g. administrated group, most of the UCNPs were excreted through feces within 48 h. Hematology, body weight, and biochemical analysis were used to further quantify the potential toxicity of the UCNPs, and results indicated that there was no over toxicity of the UCNPs in mice at the tested period. This work suggests that the clearance and excretion capabilities of PEI@UCNPs are particularly dependent on their administration routes.

SPIO-labeled Yttrium Microspheres for MR Imaging Quantification of Transcatheter Intrahepatic Delivery in a Rodent Model.

PURPOSE: To investigate the qualitative and quantitative impacts of labeling yttrium microspheres with increasing amounts of superparamagnetic iron oxide (SPIO) material for magnetic resonance (MR) imaging in phantom and rodent models. MATERIALS AND METHODS: Animal model studies were approved by the institutional Animal Care and Use Committee. The r2* relaxivity for each of four microsphere SPIO compositions was determined from 32 phantoms constructed with agarose gel and in eight concentrations from each of the four compositions. Intrahepatic transcatheter infusion procedures were performed in rats by using each of the four compositions before MR imaging to visualize distributions within the liver. For quantitative studies, doses of 5, 10, 15, or 20 mg 2% SPIO-labeled yttrium microspheres were infused into 24 rats (six rats per group). MR imaging R2* measurements were used to quantify the dose delivered to each liver. Pearson correlation, analysis of variance, and intraclass correlation analyses were performed to compare MR imaging measurements in phantoms and animal models. RESULTS: Increased r2* relaxivity was observed with incremental increases of SPIO microsphere content. R2* measurements of the 2% SPIO-labeled yttrium microsphere concentration were well correlated with known phantom concentrations (R(2) = 1.00, P < .001) over a broader linear range than observed for the other three compositions. Microspheres were heterogeneously distributed within each liver; increasing microsphere SPIO content produced marked signal voids. R2*-based measurements of 2% SPIO-labeled yttrium microsphere delivery were well correlated with infused dose (intraclass correlation coefficient, 0.98; P < .001). CONCLUSION: MR imaging R2* measurements of yttrium microspheres labeled with 2% SPIO can quantitatively depict in vivo intrahepatic biodistribution in a rat model.

Synthesis, Characterization, and Application of Core-Shell Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm) Nanoparticle as Trimodal (MRI, PET/SPECT, and Optical) Imaging Agents.

Multimodal nanoparticulate materials are described, offering magnetic, radionuclide, and fluorescent imaging capabilities to exploit the complementary advantages of magnetic resonance imaging (MRI), positron emission tomography/single-photon emission commuted tomography (PET/SPECT), and optical imaging. They comprise Fe3O4@NaYF4 core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm). These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r2) up to 326 mM(-1) s(-1) at 3T, a high affinity to [(18)F]-fluoride or radiometal-bisphosphonate conjugates (e.g., (64)Cu and (99m)Tc), and fluorescent emissions from 500 to 800 nm under excitation at 980 nm. The biodistribution of intravenously administered particles determined by PET/MR imaging suggests that negatively charged Co0.16Fe2.84O4@NaYF4(Yb, Er)-BP-PEG (10K) NPs cleared from the blood pool more slowly than positively charged NPs Fe3O4@NaYF4(Yb, Tm)-BP-PEG (2K). Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.

Synthesis of NaYF4 and NaLuF4 Based Upconversion Nanocrystals and Comparison of Their Properties.

In this study, four kinds of upconversion nanocrystals (UCNs) have been successfully synthesized by a facile solvothermal method. The morphology, crystalline phase, composition, grain size, upconversion luminescence and cell image of the UCNs were investigated. The properties of the NaLuF4-based UCNs were compared with the counterparts of NaYF4-based UCNs. It is found that the NaLuF4-based UCNs are apt to form hexagonal phase structures, while NaYF4-based UCNs of NaYF4:Yb, Er and NaYF4:Gd, Yb, Er are cubic and hexagonal phases respectively. The upconversion emission intensities of the NaLuF4-based UCNs are higher than that of NaYF4-based UCNs, and Gd3+ presented UCNs are higher than that of Gd3+ absented UCNs. The bioimaging application of NaLuF4:Gd, Yb, Er shows that bright upconversion luminescence can be observed when UCNs-labeled HeLa cells are excited with 980 nm light.

Doxorubicin-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers for NIR-triggered photodynamic therapy and enhanced chemotherapy in drug-resistant breast cancers.

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.

Biodistribution of sub-10 nm PEG-modified radioactive/upconversion nanoparticles.

The biodistribution of lanthanide-based upconversion nanophosphors (UCNPs) has attracted increasing attention, and all of the reported UCNPs display metabolism in the liver and spleen mainly. Herein, ∼8 nm poly(ethylene glycol) (PEG)-coated NaYF4 nanoparticles codoped with Yb(3+), Er(3+), and (or) radioactive (153)Sm(3+) ions were synthesized, through a hydrothermal synthetic system assisted by binary cooperative ligands with oleic acid and PEG dicarboxylic acids. The as-prepared PEG-coating NaYF4:Yb,Er and NaYF4:Yb,Er,(153)Sm are denoted as PEG-UCNPs and PEG-UCNPs((153)Sm), respectively. PEG-UCNPs were characterized by transmission electron microscope (TEM), X-ray diffraction (XRD) analysis, and Fourier-transform infrared (FTIR) spectroscopy. The PEG-UCNPs showed excellent water solubility with a hydrodynamic diameter of ∼10 nm and displayed upconversion luminescence (UCL) under continuous-wave excitation at 980 nm. At the same time, the (153)Sm-doped nanoparticles PEG-UCNPs((153)Sm) displayed radioactivity, and time-dependent biodistribution of PEG-UCNPs((153)Sm) was investigated, through single-photon emission computed tomography (SPECT) imaging and γ-counter analysis. Interestingly, PEG-UCNPs((153)Sm) had a long blood retention time and were partly eliminated through urinary pathways in vivo. Therefore, the concept of fabricating PEG-coated, small nanosize (sub-10 nm) nanoparticles with radioactive property is a useful strategy for providing a potential method to monitor lanthanide nanoparticles renal clearable.

A facile synthesis of strong near infrared fluorescent layered double hydroxide nanovehicles with an anticancer drug for tumor optical imaging and therapy.

In this work, a new multifunctional nanovehicle for tumor optical imaging and therapy was developed using Y2O3:Er(3+),Yb(3+) nanoparticles as near infrared fluorescent nanophosphors, and MgAl-layered double hydroxide (LDH) nanosheets as anticancer drug nanovehicles. Monodispersed Y2O3:Er(3+),Yb(3+) nanophosphors were readily synthesized by the urea assisted homogenous precipitation method. Hierarchically structured LDH nanosheets intercalated with an anticancer drug, fluorouracil (5FU), were deposited on the surface of Y2O3:Er(3+),Yb(3+)@SiO2 by a simple precipitation method followed by hydrothermal treatment. The resultant Y2O3:Er(3+),Yb(3+)@SiO2@LDH-5FU nanovehicles exhibit strong red upconversion fluorescence under the excitation of a 980 nm laser, which allows tracking of the nanovehicles after localization in cancer cells. A better anticancer efficiency was obtained over the nanovehicles than the free drug which can be attributed to their positively charged surfaces for favorable interaction with the negatively charged cell membranes. The multifunctional nanovehicles designed in this work are expected to be promising material candidates for simultaneous tumor optical imaging and therapy.