Integration of Au Nanosheets and GdOF:Yb,Er for NIR-I and NIR-II Light-Activated Synergistic Theranostics.

The local hyperthermia (>41 °C) effect of photothermal therapy (PTT) is significantly limited by the efficiency of PTT agents to convert laser energy to heat, and such oncotherapy, similar to conventional chemotherapy, invariably encounters the challenge of nonspecific application. Undue reliance on oxygen sources still poses particular difficulties in photodynamic therapy (PDT) for deep-level clinical applications. Considering these therapeutic issues, in this study, we constructed a versatile but unique nanosystem by encapsulating Au nanosheets in codoped gadolinium oxyfluoride (GdOF):Yb,Er spheres, followed by decoration of a chemotherapeutic drug (doxorubicin), photosensitizer (rose Bengal, RB), and targeted agent (folic acid). This allowed the incorporation of cancer treatment and real-time curative efficacy monitoring into one single theranostic nanoplatform. Benefiting from the dual contribution of the strong absorptions in the NIR-I and NIR-II regions, relevant photothermal-conversion efficiency (η) values pertaining to that final product were 39.2% at 1064 nm irradiation and 35.7% at 980 nm illumination. The fluorescence resonance energy transfer that occurred in the up-converted GdOF:Yb,Er to RB contributed to the high PDT efficacy. Combined with a micromeric acid-responsive drug release in a targeted tumor microenvironment, high-performance synergistic therapy was realized. In addition, up-conversion fluorescence imaging and computed tomography imaging accompanied by multimodal magnetic resonance imaging were simultaneously achieved owing to the doped lanthanide ions and the encapsulated Au nanosheets. Our designed oncotherapy nanosystem provides an alternative strategy to acquire ideal theranostic effects.

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.

Yb3+, Er3+ Codoped Cerium Oxide Upconversion Nanoparticles Enhanced the Enzymelike Catalytic Activity and Antioxidative Activity for Parkinson's Disease Treatment.

Oxidative stress plays an important role in Parkinson's disease (PD) and is considered a therapeutic target for PD. However, most therapeutic antioxidants show limitations due to their low reactive oxygen species (ROS) catalytic properties and low crossing of blood-brain barrier. Herein, the antioxidative activity of Yb3+ and Er3+ double-doped CeO2-x (Yb/Er/CeO2-x) upconversion nanoparticles (UCNPs) is obtained for PD treatment. Doping of Yb3+ and Er3+ ions increases oxygen vacancies, which leads to higher enzymelike catalytic activities compared to CeO2-x nanoparticles alone. Tyrosine hydroxylase protein and glial fibrillary acidic protein expression in substantia nigra and striatum as well as the open-field activity test indicates that Yb/Er/CeO2-x is effective for treatment of PD. The activities of glutathione peroxidase and total antioxidant capacity increase and the production of ROS decreases with Yb/Er/CeO2-x UCNP treatment compared with MPTP-induced injury. This indicates that the mechanism of PD treatment is to catalyze ROS products. There have been no reports to date on the usage of Yb/Er/CeO2-x as an antioxidant for PD treatment. Yb/Er/CeO2-x UCNPs cross the blood-brain barrier and exhibit biocompatibility and antioxidant catalytic properties, which decrease the ROS and effectively help in treating PD.

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.

Unmodified Rose Bengal photosensitizer conjugated with NaYF4:Yb,Er upconverting nanoparticles for efficient photodynamic therapy.

In photodynamic therapy (PDT), photosensitizer (PS) molecules are irradiated by light to generate reactive oxygen species (ROS), the presence of which subsequently leads to cell death. At present, the modality is limited to the treatment of skin diseases because of the low tissue penetration of visible or ultraviolet light required for producing ROS. To increase tissue penetration and extend the therapeutic possibilities of PDT to the treatment of deep-seated cancer, rare-earth doped nanoparticles capable of up-converting infrared to visible light are investigated. These up-converting nanoparticles (UCNPs) are conjugated with PS molecules to efficiently generate ROS. In this work, we employ hexagonal ß-NaYF4:Yb3 + ,Er3 + as UCNPs and Rose Bengal (RB) as PS molecules and demonstrate efficient in vitro PDT using this nanoformulation. Covalent bonding of the RB molecules is accomplished without their functionalization-an approach which is expected to increase the efficiency of ROS generation by 30%. Spectroscopic studies reveal that our approach results in UCNP surface fully covered with RB molecules. The energy transfer from UCNPs to RB is predominantly non-radiative as evidenced by luminescence lifetime measurements. As a result, ROS are generated as efficiently as under visible light illumination. The in vitro PDT is tested on murine breast 4T1 cancer cells incubated with 250 µg ml-1 of the nanoparticles and irradiated with NIR light under power density of 2 W cm-2 for 10 minutes. After 24 hours, the cell viability decreased to 33% demonstrating a very good treatment efficiency. These results are expected to simplify the protocols for preparation of the PDT agents and lead to improved therapeutic effects.

Ytterbium increases transmembrane water transport in Zea mays roots via aquaporin modulation.

In our study, the rare earth element ytterbium (Yb3+) was demonstrated to affect water exchange in roots of Zea mays seedlings. Herewith, the overall membrane permeability (Pd) increased. The Pd increase was determined by aquaporin activity but not the membrane lipid component since the closure of aquaporin channels due to low intracellular pH abolished the positive effect of Yb3+ on Pd. Additionally, the expression level of aquaporin genes ZmPIP2;2, ZmPIP2;6 and ZmTIP2;2 was increased when plants were grown in the presence of Yb3+. Our results indicate that previously described positive influence of rare earth metals on plant growth and productivity may be mediated (at least partially) by the modification of the plant hydraulic system.

Dual red-NIR luminescent EuYb heterolanthanide nanoparticles as promising basis for cellular imaging and sensing.

The present work introduces ternary Ln(III) (Ln = Eu, Yb, Lu) complexes with thenoyltriflouro1,3-diketonate (TTA-) and phosphine oxide derivative (PhO) as building blocks for core-shell nanoparticles with both Eu(III)- or Yb(III)-centered luminescence and the dual Eu(III)-Yb(III)-centered luminescence. Solvent-mediated self-assembly of the complexes is presented herein as the procedure for formation of EuLu, EuYb and YbLu heterometallic or homometallic cores coated by hydrophilic polystyrenesulfonate-based shells. Steady state and time resolved Eu-centered luminescence in homolanthanide and heterolanthanide EuLu and EuYb cores is affected by Eu → Eu and Eu → Yb energy transfer due to a close proximity of the lanthanide blocks within the core of nanoparticles. The Eu → Yb energy transfer is highlighted to be the reason for the enhancement of the NIR Yb-centered luminescence. Efficient cellular uptake, low cytotoxicity towards normal and cancer cells, and sensing ability of EuYb nanoparticles on lomefloxacin additives via both red and NIR channels make them promising as cellular imaging agents and sensors.

Amine-functionalized, porous silica-coated NaYF4:Yb/Er upconversion nanophosphors for efficient delivery of doxorubicin and curcumin.

Upconversion nanoparticles (UCNP) with unique multi-photon excitation photo-luminescence properties have been extensively explored as novel contrast agents for low-background biomedical imaging. There is an increasing interest in employing UCNPs as carrier for drug delivery as these offers a unique opportunity to combine therapy and diagnostics in one platform (theranostics). In the present work, we report microwave-assisted synthesis of hexagonal NaYF4:Yb/Er UCNPs coated with porous silica and functionalized with amine (UCNP@mSiO2). The UCNP@mSiO2 were investigated for controlled delivery of a chemotherapeutic agent, doxorubicin (DOX, hydrophilic), and a chemosensitizing agent, curcumin (CCM, hydrophobic). The drug loading was relatively higher for DOX (17.4%), in comparison to CCM (8.1%). The cumulative drug release from DOX-loaded UCNP@mSiO2 were 30 and 41% at physiological (7.4) and tumoral (6.4) pH, following a pseudo Fickian release pattern, whereas the release from CCM-loaded UCNP@mSiO2 were 27 and 50% at pH 7.4 and 6.4, following a non-Fickian and pseudo-Fickian release patterns, respectively. Both DOX and CCM-loaded UCNP@mSiO2 exhibited pH-dependent controlled drug delivery but the effect was more pronounced for CCM, the hydrophobic chemosensitizer. Cell viability assay using HeLa cells showed that DOX-loaded UCNP@mSiO2 inhibit cell growth in a dose-dependent manner, similar to free DOX, but the cell inhibition activity of free CCM was lower than CCM passively entrapped in UCNP@mSiO2. Confocal microscopy studies revealed cell uptake of both the drug by HeLa cells. Thus, UCNP@mSiO2 exhibited the unique capability to deliver hydrophilic and hydrophobic drugs, individually. UCNP@mSiO2 carrier, equipped with theranostic capabilities, may potentially be used for pH-responsive release of chemotherapeutic agents in cancer environment.

Green synthesis of highly dispersed ytterbium and thulium co-doped sodium yttrium fluoride microphosphors for in situ light upconversion from near-infrared to blue in animals.

We report a simple, low cost and environmentally friendly method to prepare NaYF4:Yb3+, Tm3+ upconversion microphosphors (UCMPs) by thermal decomposition of rare earth-trifluoroacetate precursors using paraffin as the high boiling non-coordinating solvent. The UCMPs exhibited cubic phase with defined shape and bright upconversion luminescence. After coating with amphiphilic polymers of phospholipid-polyethylene glycol, the NaYF4:Yb3+, Tm3+ UCMPs were highly dispersed in aqueous solutions and exhibited low cytotoxicity. Furthermore, we explored the use of the micro-injected micro-sized NaYF4:Yb3+, Tm3+ particles for converting of near infrared into blue light in mice brain. The in vivo macroscopic upconversion luminescence imaging results showed that UCMPs located at 1mm depth in the brain could be clearly distinguished. Microscopic upconversion luminescence imaging of the brain sections in vitro revealed that the UCMPs embedded at the particular location in brain tissues of mice were stable without significant diffusion in two weeks.

Phthalocyanine-Conjugated Upconversion NaYF4 :Yb3+ /Er3+ @SiO2 Nanospheres for NIR-Triggered Photodynamic Therapy in a Tumor Mouse Model.

Photodynamic therapy (PDT) has garnered immense attention as a minimally invasive clinical treatment modality for malignant cancers. However, its low penetration depth and photodamage of living tissues by UV and visible light, which activate a photosensitizer, limit the application of PDT. In this study, monodisperse NaYF4 :Yb3+ /Er3+ nanospheres 20 nm in diameter, that serve as near-infrared (NIR)-to-visible light converters and activators of a photosensitizer, were synthesized by high-temperature co-precipitation of lanthanide chlorides in a high-boiling organic solvent (octadec-1-ene). The nanoparticles were coated with a thin shell (≈3 nm) of homogenous silica via the hydrolysis and condensation of tetramethyl orthosilicate. The NaYF4 :Yb3+ /Er3+ @SiO2 particles were further functionalized by methacrylate-terminated groups via 3-(trimethoxysilyl)propyl methacrylate. To introduce a large number of reactive amino groups on the particle surface, methacrylate-terminated NaYF4 :Yb3+ /Er3+ @SiO2 nanospheres were modified with a branched polyethyleneimine (PEI) via Michael addition. Aluminum carboxyphthalocyanine (Al Pc-COOH) was then conjugated to NaYF4 :Yb3+ /Er3+ @SiO2 -PEI nanospheres via carbodiimide chemistry. The resulting NaYF4 :Yb3+ /Er3+ @SiO2 -PEI-Pc particles were finally modified with succinimidyl ester of poly(ethylene glycol) (PEG) in order to alleviate their future uptake by the reticuloendothelial system. Upon 980 nm irradiation, the intensive red emission of NaYF4 :Yb3+ /Er3+ @SiO2 -PEI-Pc-PEG nanoparticles completely vanished, indicating efficient energy transfer from the nanoparticles to Al Pc-COOH, which generates singlet oxygen (1 O2 ). Last but not least, NaYF4 :Yb3+ /Er3+ @SiO2 -PEI-Pc-PEG nanospheres were intratumorally administered into mammary carcinoma MDA-MB-231 growing subcutaneously in athymic nude mice. Extensive necrosis developed at the tumor site of all mice 24-48 h after irradiation by laser at 980 nm wavelength. The results demonstrate that the NaYF4 :Yb3+ /Er3+ @SiO2 -PEI-Pc-PEG nanospheres have great potential as a novel NIR-triggered PDT nanoplatform for deep-tissue cancer therapy.

Imaging cellular trafficking processes in real time using lysosome targeted up-conversion nanoparticles.

ß-NaYF4:Yb,Gd up-conversion nanoparticles, UCNPs, surface functionalized with suitable targetting peptides function as nontoxic lysosome-specific imaging probes.

Multifunctional BaYbF5: Gd/Er upconversion nanoparticles for in vivo tri-modal upconversion optical, X-ray computed tomography and magnetic resonance imaging.

Development of high-quality upconversion nanoparticles (UCNPs) with combination of the merits of multiple molecular imaging techniques, such as, upconversion luminescence (UCL) imaging, X-ray computed tomography (CT), and magnetic resonance (MR) imaging, could significantly improve the accuracy of biological diagnosis. In this work, multifunctional BaYbF5: Gd/Er (50:2mol%) UCNPs were synthesized via a solvothermal method using oleic acid (OA) as surface ligands (denoted as OA-UCNPs). The OA-UCNPs were further treated by diluted HCl to form ligand-free UCNPs (LF-UCNPs) for later bioimaging applications. The cytotoxicity assay in HeLa cells shows low cell toxicity of these LF-UCNPs. Owing to the efficient UCL of BaYbF5: Gd/Er, the LF-UCNPs were successfully used as luminescent bioprobe in UCL bioimaging. And, X-ray CT imaging reveals that BaYbF5: Gd/Er UCNPs can act as potential contrast agents for detection of the liver and spleen in the live mice owing to the high-Z elements (e.g., Ba, Yb, and Gd) in host matrix. Moreover, with the addition of Gd, the as-designed UCNPs exhibit additional positive contrast enhancement in T1-weighted MR imaging. These findings demonstrate that BaYbF5: Gd/Er UCNPs are potential candidates for tri-modal imaging.

Ultrasmall, water dispersible, TWEEN80 modified Yb:Er:NaGd(WO4)2 nanoparticles with record upconversion ratiometric thermal sensitivity and their internalization by mesenchymal stem cells.

This work presents the synthesis by coprecipitation of diamond shaped Yb:Er:NaGd(WO4)2 crystalline nanoparticles (NPs) with diagonal dimensions in the 5-7 nm × 10-12 nm range which have been modified with TWEEN80 for their dispersion in water, and their interaction with mesenchymal stem cells (MSCs) proposed as cellular NP vehicles. These NPs belong to a large family of tetragonal Yb:Er:NaT(XO4)2 (T = Y, La, Gd, Lu; X = Mo, W) compounds with green (2H11/2 + 4S3/2 â†’ 4I15/2) Er-related upconversion (UC) efficiency comparable to that of Yb:Er:ß-NaYF4 reference compound, but with a ratiometric thermal sensitivity (S) 2.5-3.5 times larger than that of the fluoride. At the temperature range of interest for biomedical applications (∼293-317 K/20-44 °C) S = 108-118 × 10-4 K-1 for 20 at%Yb:5 at%Er:NaGd(WO4)2 NPs, being the largest values so far reported using the 2H11/2/4S3/2 Er intensity ratiometric method. Cultured MSCs, incubated with these water NP emulsions, internalize and accumulate the NPs enclosed in endosomes/lysosomes. Incubations with up to 10 µg of NPs per ml of culture medium maintain cellular metabolism at 72 h. A thermal assisted excitation path is discussed as responsible for the UC behavior of Yb:Er:NaT(XO4)2 compounds.

Technical Note: Impact of cell repopulation and radionuclide uptake phase on cell survival.

PURPOSE: To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical. METHODS: The instantaneous-uptake model of O'Donoghue ["The impact of tumor cell proliferation in radioimmunotherapy," Cancer 73, 974-980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED). RESULTS: Surviving fractions are calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1-24 h, extrapolated initial dose-rates 0.5-1 Gy h(-1), and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and α-coefficient equal to 0.3 and 0.5 Gy(-1). It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger α-coefficient. CONCLUSIONS: The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy.

A chimeric protein of aluminum-activated malate transporter generated from wheat and Arabidopsis shows enhanced response to trivalent cations.

TaALMT1 from wheat (Triticum aestivum) and AtALMT1 from Arabidopsis thaliana encode aluminum (Al)-activated malate transporters, which confer acid-soil tolerance by releasing malate from roots. Chimeric proteins from TaALMT1 and AtALMT1 (Ta::At, At::Ta) were previously analyzed in Xenopus laevis oocytes. Those studies showed that Al could activate malate efflux from the Ta::At chimera but not from At::Ta. Here, functions of TaALMT1, AtALMT1 and the chimeric protein Ta::At were compared in cultured tobacco BY-2 cells. We focused on the sensitivity and specificity of their activation by trivalent cations. The activation of malate efflux by Al was at least two-fold greater in the chimera than the native proteins. All proteins were also activated by lanthanides (erbium, ytterbium, gadolinium, and lanthanum), but the chimera again released more malate than TaALMT1 or AtALMT1. In Xenopus oocytes, Al, ytterbium, and erbium activated inward currents from the native TaALMT1 and the chimeric protein, but gadolinium only activated currents from the chimera. Lanthanum inhibited currents from both proteins. These results demonstrated that function of the chimera protein was altered compared to the native proteins and was more responsive to a range of trivalent cations when expressed in plant cells.

Cytotoxic interactions of bare and coated NaGdF4:Yb(3+):Er(3+) nanoparticles with macrophage and fibroblast cells.

The lanthanide nano-compounds are well suited to serve as fluorescent and magnetic contrast agents and luminescent labels. Although they are considered as promising materials for bio-imaging and bio-sensors in vivo or in vitro, the amount of data is still insufficient for deep understanding the toxicity of these nanomaterials. This knowledge is of great importance in the light of growing use of the biofunctionalized nanoparticles, which raises some questions about safety of these materials. Despite lanthanide-doped NaGdF4 nanocrystals are considered as non-toxic, here we present the data showing the fatal effect of newly synthetized NaGdF4:Yb(3+):Er(3+) on chosen types of cells. Our studies were performed on two cell lines NIH3T3 fibroblasts, and RAW264.7 macrophages. Cytotoxic properties of NaGdF4:Yb(3+):Er(3+) nanoparticles and their biological effects were studied by assessing cell culture viability (MTS), proliferation and apoptosis. Bare NaGdF4:Yb(3+):Er(3+) nanocrystals were cytotoxic and induced apoptosis of both NIH3T3 and RAW264.7 cells. Their cytotoxicity was reduced by PEGylation, at the expense of minimizing direct interactions between the compound and the cell. On the other hand, coating with silica reduced cell death induced by Yb(3+):Er(3+) codoped NaGdF4 nanocrystals (but proliferation was still inhibited). The NH2-modified silica coated nanoparticles were clearly less cytotoxic than pristine nanoparticles, which suggests that both, silica and PEG coatings are reasonable approaches to decrease cytotoxicity of the nanocrystal labels. The silica and PEG shell, should also enable and simplify further bio-functionalization of these luminescent labels. The authors acknowledge the financial support from: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences (IITD PAN) grant no. 3/15, Polish Ministry of Science and Higher Education, Grant N N507 499538 and from the Wroclaw Research Centre EIT+ within the project "The Application of Nanotechnology in Advanced Materials" - NanoMat (POIG.01.01.02-02-002/08) financed by the European Regional Development Fund (Operational Program Innovative Economy, 1.1.2).

Functional up-converting SrTiO3:Er(3+)/Yb(3+) nanoparticles: structural features, particle size, colour tuning and in vitro RBC cytotoxicity.

SrTiO3 nanoparticles co-doped with a broad concentration range of Er(3+) and Yb(3+) ions were fabricated using the citric route as a function of annealing temperatures of 500-1000 °C. The effect of a broad co-dopant concentration range and sintering temperature on structural and up-conversion properties was investigated in detail by X-ray diffraction techniques and optical spectroscopy. The TEM technique was used to estimate the mean particle size, which was around 30 nm for the inorganic product annealed at 600 °C. Up-conversion emission color tuning was achieved by particle size control. Power dependence of the green and red emissions was found to be a result of temperature determination in the operating range of SrTiO3 nanoparticles and a candidate for the fast and local microscopic heating and heat release induced by IR irradiation. The color changed from white-red-yellow-green upon an increase of sintering temperature, inducing changes in the surface-to-volume ratio and the number of optically active ions in particle surface regions. The cytotoxic activity of nanoparticles on human red blood cells was investigated, showing no harmful effects up to a particle concentration of 0.1 mg ml(-1). The cytotoxic response of a colloidal suspension of nanoparticles to RBC cells was connected with the strong affinity of SrTiO3 particles to the cell membranes, blocking the transport of important biological solutes.

Multifunctional lanthanide and silver ion co-doped nano-chlorapatites with combined spectroscopic and antimicrobial properties.

Nanocrystalline chlorapatites (Ca10(PO4)6Cl2) doped with lanthanide ions (Eu(3+), Er(3+) and Yb(3+)) and co-doped with silver ions (Ag(+)) were synthesized by a hydrothermal synthesis route. XRD, TEM, and SAED measurements indicated that the powders are single phased and crystallize with a hexagonal structure with good dispersion. The results showed well crystallized chlorapatite grains with a diameter of about 45 nm. The antimicrobial activity of the nanoparticles against Escherichia coli ATCC 11229 and ATCC 25922, Klebsiella pneumoniae ATCC 700603, and Pseudomonas aeruginosa PAO1 and ATCC 27853 was studied. The best activity was observed for the Eu(3+),Ag(+):Ca10(PO4)6Cl2 and Eu(3+),Ag(+),Yb(3+):Ca10(PO4)6Cl2 compositions. These multifunctional nanocrystalline powders could be used as a promising antimicrobial agent and material for bio-detection.

Synthesis of YF3: Yb, Er upconverting nanofluorophores using chitosan and their cytotoxicity in MCF-7 cells.

In this work, we described one pot hydrothermal synthesis of surface modified water soluble YF3: Yb, Er upconverting nanofluorophores (UCNFs) using natural biopolymer chitosan. The obtained nanocrystals have undergone X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), high resolution transmission electron microscopy (HRTEM) and photoluminescence (PL) studies. The nanoparticles possess uniform particle size distribution with average size about 27 nm. The cytotoxicity results revealed that the chitosan capped nanoparticles exhibit excellent biocompatibility in human breast cancer cells. In conclusion, the water soluble chitosan capped YF3: Yb, Er nanoparticles could be used as a potential candidate in bio-imaging and therapeutic applications.

The influence of NaYF4:Yb,Er size/phase on the multimodality of co-encapsulated magnetic photon-upconverting polymeric nanoparticles.

We report the synthesis, characterisation and evaluation of the in vitro biocompatibility of polymeric nanoparticles with both magnetic and upconverting fluorescent properties. The particles consist of superparamagnetic iron oxide nanoparticles and upconverting NaYF4:Yb,Er nanoparticles co-encapsulated within a poly(glycidyl methacrylate) sphere. Two different upconverting nanoparticles (10 nm α-NaYF4:Yb,Er and 50 nm ß-NaYF4:Yb,Er) were synthesised and the optical and magnetic properties of the composite polymeric nanoparticle systems assessed by near infra-red laser spectroscopy, SQUID magnetometry and proton relaxometry. A live-dead assay was used to assess the viability of PC-12 neural cells incubated with varying concentrations of the nanoparticles. The composite nanoparticles produced no observed impact on cellular viability even at concentrations as high as 1000 µg mL(-1). Confocal microscopy revealed uptake of nanoparticles by PC-12 cells and peri-nuclear cytoplasmic localisation. Both particle systems show favourable magnetic properties. However, only the nanospheres containing 50 nm ß-NaYF4:Yb,Er were suitable for optical tracking because the presence of iron oxide within the composites imparts a significant quenching of the upconversion emission. This study demonstrates the size and phase of the upconverting nanoparticles are important parameters that have to be taken into account in the design of multimodal nanoparticles using co-encapsulation strategies.