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2.
ACS Appl Mater Interfaces ; 13(24): 27895-27903, 2021 Jun 23.
Article En | MEDLINE | ID: mdl-34101418

Phototherapy holds great promise in the treatment of bacterial infections, especially the multidrug resistant bacterial infections. However, most therapeutic agents are based on the integration of individual photothermal agents and photosensitizers, always in the activated state, and generally lack bacterial specificity, resulting in uncertain pharmacokinetics and serious nonspecific damage to normal tissues. Herein, we report a pH-responsive nanoplatform with synergistic chemo-phototherapy function for smart fluorescence imaging-guided precision sterilization. pH reversible activated symmetric cyanine was designed and prepared as a bacterial-specific imaging unit and PTT/PDT-in-one agent. Meanwhile, a guanidinium-based covalent organic framework (COF) was employed as a nanocarrier and chemotherapy agent to build the intelligent nanoplatform via electrostatic self-assembly. The self-assembly of the PTT/PDT-in-one agent and the COF greatly improves the stability and blood circulation of the PTT/PDT-in-one agent and provides charge-reversed intelligent targeting ability. The developed smart nanoplatform not only enables bacterial-targeted imaging but also possesses chemo/PTT/PDT synergetic high-efficiency bactericidal effects with little side effects, showing great potential in practical applications.


Anti-Bacterial Agents/therapeutic use , Fluorescent Dyes/therapeutic use , Metal-Organic Frameworks/therapeutic use , Photosensitizing Agents/therapeutic use , Staphylococcal Infections/diagnostic imaging , Staphylococcal Infections/drug therapy , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/radiation effects , Escherichia coli/drug effects , Female , Fluorescent Dyes/chemistry , Fluorescent Dyes/radiation effects , Gadolinium/chemistry , Gadolinium/radiation effects , Indoles/chemistry , Indoles/radiation effects , Infrared Rays , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/radiation effects , Mice, Inbred BALB C , Microbial Sensitivity Tests , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/radiation effects , Photothermal Therapy , Precision Medicine/methods , Singlet Oxygen/metabolism , Staphylococcus aureus/drug effects
3.
ACS Appl Mater Interfaces ; 12(51): 56874-56885, 2020 Dec 23.
Article En | MEDLINE | ID: mdl-33326207

Radiotherapy is the main treatment for cancer patients. A major concern in radiotherapy is the radiation resistance of some tumors, such as human nonsmall cell lung cancer. However, the radiation dose delivered to the tumors is often limited by the possibility of collateral damage to surrounding healthy tissues. A new and efficient gadolinium-based nanoparticle, AGuIX, has recently been developed for magnetic resonance imaging-guided radiotherapy and has been proven to act as an efficient radiosensitizer. The amplified radiation effects of AGuIX nanoparticles appear to be due to the emission of low-energy photoelectrons and Auger electron interactions. We demonstrated that AGuIX nanoparticles exacerbated radiation-induced DNA double-strand break damage and reduced DNA repair in the H1299 nonsmall cell lung cancer cell line. Furthermore, we observed a significant improvement in tumor cell damage and growth suppression, under radiation therapy, with the AGuIX nanoparticles in a H1299 mouse xenograft model. This study paves the way for research into the radiosensitization mechanism of AGuIX nanoparticles and provides a scientific basis for the use of AGuIX nanoparticles as radiosensitizing drugs.


Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Metal Nanoparticles/therapeutic use , Radiation-Sensitizing Agents/therapeutic use , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/radiation effects , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , DNA Breaks, Double-Stranded/drug effects , DNA Repair/drug effects , Gadolinium/chemistry , Gadolinium/radiation effects , Humans , Lung/pathology , Lung Neoplasms/pathology , Male , Metal Nanoparticles/chemistry , Metal Nanoparticles/radiation effects , Mice, Nude , Radiation, Ionizing , Radiation-Sensitizing Agents/chemistry , Radiation-Sensitizing Agents/radiation effects , Xenograft Model Antitumor Assays
4.
ACS Appl Mater Interfaces ; 12(23): 25604-25615, 2020 Jun 10.
Article En | MEDLINE | ID: mdl-32406668

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.


Anti-Bacterial Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Paraquat/therapeutic use , Staphylococcal Infections/drug therapy , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Bridged-Ring Compounds/chemistry , Bridged-Ring Compounds/toxicity , Cell Line, Tumor , Escherichia coli/drug effects , Female , Fluorides/chemistry , Fluorides/radiation effects , Gadolinium/chemistry , Gadolinium/radiation effects , Hyaluronic Acid/chemistry , Hyaluronic Acid/toxicity , Imidazoles/chemistry , Imidazoles/toxicity , Infrared Rays , Mice, Inbred C57BL , Microbial Sensitivity Tests , Nanoparticles/chemistry , Nanoparticles/radiation effects , Nanoparticles/toxicity , Paraquat/chemistry , Paraquat/toxicity , Polyesters/chemistry , Polyesters/toxicity , Staphylococcus aureus/drug effects , Thulium/chemistry , Thulium/radiation effects , Ytterbium/chemistry , Ytterbium/radiation effects , Zebrafish
5.
Mikrochim Acta ; 187(6): 317, 2020 05 08.
Article En | MEDLINE | ID: mdl-32385722

The effect of novel silver nanowire encapsulated NaGdF4:Yb,Er hybrid nanocomposite on the upconversion emission and bioimaging properties has been investigated. The upconvension nanomaterials were synthesised by polyol method in the presence of ethylene glycol, PVP and ethylenediamine. The NaGdF4:Yb,Er-Ag hybrid was formed with upconverting NaGdF4:Yb,Er nanoparticles of size ~ 80 nm and silver nanowires of thickness ~ 30 nm. The surface plasmon induced by the silver ion in the NaGdF4:Yb,Er-Ag nanocomposite resulted an intense upconversion green emission at 520 nm and red emission at 660 nm by NIR diode laser excitation at 980 nm wavelength. The UV-Vis-NIR spectral absorption at 440 nm and 980 nm, the intense Raman vibrational modes and the strong upconversion emission results altogether confirm the localised surface plasmon resonance effect of silver ion in the hybrid nanocomposite. MRI study of both NaGdF4:Yb,Er nanoparticle and NaGdF4:Yb,Er-Ag nanocomposite revealed the T1 relaxivities of 22.13 and 10.39 mM-1 s-1, which are larger than the commercial Gd-DOTA contrast agent of 3.08 mM-1 s-1. CT imaging NaGdF4:Yb,Er-Ag and NaGdF4:Yb,Er respectively showed the values of 53.29 HU L/g and 39.51 HU L/g, which are higher than 25.78 HU L/g of the CT contrast agent Iobitridol. The NaGdF4:Yb,Er and NaGdF4:Yb,Er-Ag respectively demonstrated a negative zeta potential of 54 mV and 55 mV, that could be useful for biological application. The in vitro cytotoxicity of the NaGdF4:Yb,Er tested in HeLa and MCF-7 cancer cell line by MTT assay demonstrated a cell viability of 90 and 80 %, respectively. But, the cell viability of NaGdF4:Yb,Er-Ag slightly decreased to 80 and 78%. The confocal microscopy imaging showed that the UCNPs are effectively up-taken inside the nucleolus of the cancer cells, and it might be useful for NIR laser-assisted phototherapy for cancer treatment. Graphical abstract.


Contrast Media/chemistry , Fluorescent Dyes/chemistry , Fluorides/chemistry , Gadolinium/chemistry , Nanocomposites/chemistry , Nanowires/chemistry , Cell Line, Tumor , Contrast Media/radiation effects , Erbium/chemistry , Erbium/radiation effects , Fluorescent Dyes/radiation effects , Fluorides/radiation effects , Gadolinium/radiation effects , Humans , Magnetic Resonance Imaging , Metal Nanoparticles/chemistry , Metal Nanoparticles/radiation effects , Microscopy, Confocal , Microscopy, Fluorescence , Nanocomposites/radiation effects , Nanowires/radiation effects , Silver/chemistry , Silver/radiation effects , Tomography, X-Ray Computed , Ytterbium/chemistry , Ytterbium/radiation effects
6.
ACS Appl Mater Interfaces ; 12(21): 23677-23688, 2020 May 27.
Article En | MEDLINE | ID: mdl-32380825

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.


Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Hydrogen/therapeutic use , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Water/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/radiation effects , Cell Line, Tumor , Copper/chemistry , Copper/radiation effects , Fluorides/chemistry , Fluorides/radiation effects , Gadolinium/chemistry , Gadolinium/radiation effects , Graphite/chemistry , Graphite/radiation effects , Humans , Hydrogen/chemistry , Hyperthermia, Induced/methods , Infrared Rays , Lasers , Mice , Nanoparticles/chemistry , Nanoparticles/radiation effects , Nitrogen Compounds/chemistry , Nitrogen Compounds/radiation effects , Photochemotherapy/methods , Reactive Oxygen Species/metabolism , Thulium/chemistry , Thulium/radiation effects , Ytterbium/chemistry , Ytterbium/radiation effects
7.
Inorg Chem ; 59(7): 4909-4923, 2020 Apr 06.
Article En | MEDLINE | ID: mdl-32162905

Photodynamic therapy (PDT) is commonly employed in clinics to treat the cancer, but because of the hypoxic tumor microenvironment prevalent inside tumors, PDT therapeutic efficiency is not adequate hence limiting the effectiveness of PDT. Therefore, we designed a nanocomposite consisting of reduced nanographene oxide (rGO) modified with polyethylene glycol (PEG), manganese dioxide (MnO2), upconversion nanoparticles (UCNPs), and Chlorin e6 (Ce6) to spark oxygen production from H2O2 with the aim of relieving the tumor hypoxic microenvironments. For in vivo tumor PDT and photothermal therapy (PTT), UCNPs-Ce6-labeled rGO-MnO2-PEG nanocomposites were used as a therapeutic agent, augmenting the therapeutic efficiency of PDT via redox progression through the catalytic H2O2 decomposition pathway and further achieving excellent tumor inhibition. It is important to mention that degradation of MnO2 in an acidic cellular microenvironment leads to the creation of a massive volume of Mn2+ which was employed as a contrast mediator for magnetic resonance imaging (MRI). Our research postulates an approach to spark O2 formation through an internal stimulus to augment the efficiency of MRI- and computerized tomography (CT)-imaging-guided PDT and PTT.


Antineoplastic Agents/therapeutic use , Nanocomposites/therapeutic use , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Photosensitizing Agents/therapeutic use , Porphyrins/therapeutic use , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Chlorophyllides , Female , Fluorides/chemistry , Fluorides/radiation effects , Fluorides/therapeutic use , Gadolinium/chemistry , Gadolinium/radiation effects , Gadolinium/therapeutic use , Graphite/chemistry , Graphite/therapeutic use , Humans , Infrared Rays , Manganese Compounds/chemistry , Manganese Compounds/therapeutic use , Mice , Nanocomposites/chemistry , Nanoparticles/chemistry , Oxides/chemistry , Oxides/therapeutic use , Oxygen/metabolism , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Polyethylene Glycols/chemistry , Polyethylene Glycols/therapeutic use , Porphyrins/chemistry , Porphyrins/radiation effects , Tumor Microenvironment/physiology , Xenograft Model Antitumor Assays
8.
Analyst ; 145(6): 2345-2356, 2020 Mar 16.
Article En | MEDLINE | ID: mdl-31993615

The use of nanoparticles (NP) as dose enhancers in radiotherapy (RT) is a growing research field. Recently, the use of NP has been extended to charged particle therapy in order to improve the performance in radioresistant tumors. However, the biological mechanisms underlying the synergistic effects involved in NP-RT approaches are not clearly understood. Here, we used the capabilities of synchrotron-based Fourier Transform Infrared Microspectroscopy (SR-FTIRM) as a bio-analytical tool to elucidate the NP-induced cellular damage at the molecular level and at a single-cell scale. F98 glioma cells doped with AuNP and GdNP were irradiated using several types of medical ion beams (proton, helium, carbon and oxygen). Differences in cell composition were analyzed in the nucleic acids, protein and lipid spectral regions using multivariate methods (Principal Component Analysis, PCA). Several NP-induced cellular modifications were detected, such as conformational changes in secondary protein structures, intensity variations in the lipid CHx stretching bands, as well as complex DNA rearrangements following charged particle therapy irradiations. These spectral features seem to be correlated with the already shown enhancement both in the DNA damage response and in the reactive oxygen species (ROS) production by the NP, which causes cell damage in the form of protein, lipid, and/or DNA oxidations. Vibrational features were NP-dependent due to the NP heterogeneous radiosensitization capability. Our results provided new insights into the molecular changes in response to NP-based RT treatments using ion beams, and highlighted the relevance of SR-FTIRM as a useful and precise technique for assessing cell response to innovative radiotherapy approaches.


Metal Nanoparticles/chemistry , Radiation-Sensitizing Agents/pharmacology , Animals , Cell Line, Tumor , Gadolinium/chemistry , Gadolinium/radiation effects , Light , Lipids/chemistry , Metal Nanoparticles/radiation effects , Microspectrophotometry/methods , Microspectrophotometry/statistics & numerical data , Nucleic Acid Conformation/drug effects , Nucleic Acids/chemistry , Nucleic Acids/drug effects , Principal Component Analysis , Protein Conformation/drug effects , Proteins/chemistry , Proteins/drug effects , Radiation-Sensitizing Agents/radiation effects , Rats , Silver/chemistry , Silver/radiation effects , Synchrotrons
9.
Analyst ; 145(2): 530-536, 2020 Jan 21.
Article En | MEDLINE | ID: mdl-31761917

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.


Coloring Agents/chemistry , Iron/blood , Luminescent Agents/chemistry , Luminescent Measurements/methods , Nanoparticles/chemistry , Fluorides/chemistry , Fluorides/radiation effects , Gadolinium/chemistry , Gadolinium/radiation effects , Humans , Indoles/chemistry , Infrared Rays , Luminescent Agents/radiation effects , Nanoparticles/radiation effects , Thulium/chemistry , Thulium/radiation effects , Ytterbium/chemistry , Ytterbium/radiation effects
10.
ACS Sens ; 3(9): 1683-1689, 2018 09 28.
Article En | MEDLINE | ID: mdl-30095257

Detection of dopamine, an important neurotransmitter, is vital for understanding its roles in mammals and disease diagnosis. However, commonly available methods for dopamine detection typically rely on a single signal readout, which can be susceptible to interference by internal or external factors. Here, we report a dual-signal detection of dopamine based on label-free luminescent NaGdF4:Tb nanoparticles. In the presence of dopamine, the NaGdF4:Tb nanoparticles exhibit luminescence quenching under the excitation of 272 nm, while they give enhanced luminescence under 297 nm excitation, realizing both turn off and turn on detection of dopamine. The nanoparticle-based dual-signal sensors exhibit high sensitivity, with a detection limit of ∼30 nM, and good selectivity, which offers the possibility to identify potential interferents in the samples. We further demonstrate that the dual-signal response results from different energy-transfer processes within the nanoparticles under the excitation of different light. The new strategy demonstrated here should pave the way for the development of multiresponse nanosensors based on lanthanide-doped luminescent nanomaterials.


Dopamine/analysis , Luminescent Agents/chemistry , Luminescent Measurements/methods , Metal Nanoparticles/chemistry , Neurotransmitter Agents/analysis , Dopamine/blood , Dopamine/radiation effects , Dopamine/urine , Energy Transfer , Gadolinium/chemistry , Gadolinium/radiation effects , Humans , Limit of Detection , Luminescence , Luminescent Agents/radiation effects , Metal Nanoparticles/radiation effects , Neurotransmitter Agents/blood , Neurotransmitter Agents/radiation effects , Neurotransmitter Agents/urine , Terbium/chemistry , Terbium/radiation effects , Ultraviolet Rays
11.
Water Sci Technol ; 74(10): 2325-2336, 2016 Nov.
Article En | MEDLINE | ID: mdl-27858789

Cerium (IV) oxide (CeO2), samarium (Sm) and gadolinium (Gd) doped CeO2 nanoparticles were prepared using microwave technique. The effect of microwave irradiation time, microwave power and pH of the starting solution on the structure and crystallite size were investigated. The prepared nanoparticles were characterized using X-ray diffraction, FT-Raman spectroscopy, and transmission electron microscope. The photocatalytic activity of the as-prepared CeO2, Sm and Gd doped CeO2 toward degradation of methylene blue (MB) dye was investigated under UV light irradiation. The effect of pH, the amount of catalyst and the dye concentration on the degradation extent were studied. The photocatalytic activity of CeO2 was kinetically enhanced by trivalent cation (Gd and Sm) doping. The results revealed that Gd doped CeO2 nanoparticles exhibit the best catalytic degradation activity on MB under UV irradiation. For clarifying the environmental safety of the by products produced from the degradation process, the pathways of MB degradation were followed using liquid chromatography/mass spectroscopy (LC/MS). The total organic carbon content measurements confirmed the results obtained by LC/MS. Compared to the same nanoparticles prepared by another method, it was found that Gd doped CeO2 prepared by hydrothermal process was able to mineralize MB dye completely under UV light irradiation.


Cerium/chemistry , Gadolinium/chemistry , Methylene Blue/chemistry , Nanoparticles/chemistry , Samarium/chemistry , Water Pollutants, Chemical/chemistry , Catalysis , Cerium/radiation effects , Coloring Agents/chemistry , Coloring Agents/radiation effects , Gadolinium/radiation effects , Methylene Blue/radiation effects , Microscopy, Electron, Transmission , Microwaves , Nanoparticles/radiation effects , Nanoparticles/ultrastructure , Samarium/radiation effects , Spectrum Analysis, Raman , Ultraviolet Rays , Water Pollutants, Chemical/radiation effects , X-Ray Diffraction
12.
Water Res ; 91: 244-50, 2016 Mar 15.
Article En | MEDLINE | ID: mdl-26802476

Since the 1980s, the broad application of gadolinium(Gd)-based contrast agents for magnetic resonance imaging (MRI) has led to significantly increased concentrations of Gd in the aqueous environment. Little is known about the stability of these highly polar xenobiotics under environmental conditions, in wastewater and in drinking water treatment. Therefore, the stability of frequently applied Gd-based MRI contrast agents towards UV radiation was investigated. The hyphenation of hydrophilic interaction liquid chromatography (HILIC) with inductively coupled plasma mass spectrometry (ICP-MS) and of HILIC with electrospray ionization mass spectrometry (ESI-MS) provided quantitative elemental information as well as structural information. The contrast agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A showed a high stability in irradiation experiments applying a wavelength range from 220 nm to 500 nm. Nevertheless, the degradation of Gd-BOPTA as well as the formation of Gd-containing transformation products was observed by means of HILIC-ICP-MS. Matrix-dependent irradiation experiments showed a degradation of Gd-BOPTA down to 3% of the initial amount in purified water after 300 min, whereas the degradation was slowed down in drinking water and surface water. Furthermore, it was observed that the sum of species continuously decreased with proceeding irradiation in all matrices. After irradiation in purified water for 300 min only 16% of the sum of species was left. This indicates a release of Gd(III) ions from the complex in course of irradiation. HILIC-ESI-MS measurements revealed that the transformation products mostly resulted from O-dealkylation and N-dealkylation reactions. In good correlation with retention times, the majority of transformation products were found to be more polar than Gd-BOPTA itself. Based on accurate masses, sum formulas were obtained and structures could be proposed.


Contrast Media/radiation effects , Gadolinium/radiation effects , Ultraviolet Rays , Waste Disposal, Fluid , Wastewater/analysis , Water Pollutants, Chemical/radiation effects , Chromatography, Liquid , Mass Spectrometry , Spectrometry, Mass, Electrospray Ionization
13.
Radiat Environ Biophys ; 54(4): 423-31, 2015 Nov.
Article En | MEDLINE | ID: mdl-26242374

Core-inner-valence ionization of high-Z nanoparticle atomic clusters can de-excite electrons through various interatomic de-excitation processes, thereby leading to the ionization of both directly exposed atoms and adjacent neutral atoms within the nanoparticles, and to an enhancement in photon-electron emission, which is termed the nanoradiator effect. To investigate the nanoradiator-mediated dose enhancement in the radio-sensitizing of high-Z nanoparticles, the production of reactive oxygen species (ROS) was measured in a gadolinium oxide nanoparticle (Gd-oxide NP) solution under core-inner-valence excitation of Gd with either 50 keV monochromatic synchrotron X-rays or 45 MeV protons. This measurement was compared with either a radiation-only control or a gadolinium-chelate magnetic resonance imaging contrast agent solution containing equal amounts of gadolinium as the separate atomic species in which Gd-Gd interatomic de-excitations are absent. Ionization excitations followed by ROS measurements were performed on nanoparticle-loaded cells or aqueous solutions. Both photoexcitation and proton impact produced a dose-dependent enhancement in the production of ROS by a range of factors from 1.6 to 1.94 compared with the radiation-only control. Enhanced production of ROS, by a factor of 1.83, was observed from Gd-oxide NP atomic clusters compared with the Gd-chelate molecule, with a Gd concentration of 48 µg/mL in the core-level photon excitation, or by a factor of 1.82 under a Gd concentration of 12 µg/mL for the proton impact at 10 Gy (p < 0.02). The enhanced production of ROS in the irradiated nanoparticles suggests the potential for additional therapeutic dose enhancements in radiation treatment via the potent Gd-Gd interatomic de-excitation-driven nanoradiator effect.


Gadolinium/chemistry , Gadolinium/radiation effects , Metal Nanoparticles/chemistry , Metal Nanoparticles/radiation effects , Reactive Oxygen Species/chemical synthesis , Reactive Oxygen Species/radiation effects , Contrast Media/chemistry , Contrast Media/radiation effects , Dose-Response Relationship, Radiation , Linear Energy Transfer/radiation effects , Materials Testing , Metal Nanoparticles/ultrastructure , Protons , Radiation Dosage , Scattering, Radiation , X-Rays
14.
Phys Med Biol ; 60(11): 4449-64, 2015 Jun 07.
Article En | MEDLINE | ID: mdl-25988839

The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist(®) in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL(-1)), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44 ± 0.33 and 1.50 ± 0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66 ± 0.17 and 1.01 ± 0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly 'energy dependent' for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs.


Contrast Media/radiation effects , Gadolinium/radiation effects , Metal Nanoparticles/radiation effects , Photons , Radiation-Sensitizing Agents/radiation effects , Animals , Cell Line, Tumor , Cell Survival/drug effects , Contrast Media/adverse effects , Metal Nanoparticles/adverse effects , Metal Nanoparticles/chemistry , Radiation-Sensitizing Agents/adverse effects , Rats , X-Rays
15.
Magn Reson Med ; 74(2): 468-73, 2015 Aug.
Article En | MEDLINE | ID: mdl-25186276

PURPOSE: To describe and quantify the different relaxation mechanisms operating in suspensions of liposomes that encapsulate paramagnetic lanthanide(III) complexes. THEORY AND METHODS: The transverse relaxation rate of lanthanide-loaded liposomes receives contribution from the exchange between intraliposomal and bulk water protons, and from magnetic susceptibility effects. Phospholipids vesicles encapsulating different Ln(III)-HPDO3A complexes (Ln = Eu, Gd, or Dy) were prepared using the conventional thin film rehydration method. Relaxation times (T1 , T2 , and T2*) were measured at 14 Tesla (T) and 25 °C. The effect of compartmentalization of the paramagnetic agent inside the liposomal cavity was evaluated by means of an IRON-modified MRI sequence. RESULTS: NMR measurements demonstrated that Curie spin relaxation is the dominant contribution (> 90%) to the observed transverse relaxation rate of paramagnetic liposomes. This was further confirmed by MRI that showed the ability of the liposome entrapped lanthanide complexes to generate IRON-MRI positive contrast in a size dependent manner. CONCLUSION: The Curie spin relaxation mechanism is by far the principal mechanism involved in the T2 shortening of the water protons in suspension of paramagnetic liposomes at 14T. The access to IRON contrast extends the potential of such nanosystems as MRI contrast agents.


Contrast Media/chemistry , Heterocyclic Compounds/chemistry , Liposomes/chemistry , Magnetic Resonance Imaging/methods , Nanocapsules/chemistry , Organometallic Compounds/chemistry , Phospholipids/chemistry , Contrast Media/radiation effects , Diffusion , Electric Impedance , Gadolinium/chemistry , Gadolinium/radiation effects , Heterocyclic Compounds/radiation effects , Lanthanum/chemistry , Lanthanum/radiation effects , Magnetic Fields , Magnetic Resonance Imaging/instrumentation , Materials Testing , Nanocapsules/ultrastructure , Organometallic Compounds/radiation effects , Phantoms, Imaging
16.
Radiat Prot Dosimetry ; 159(1-4): 233-6, 2014 Jun.
Article En | MEDLINE | ID: mdl-24795394

This paper continues analyses on organic compounds for application in neutron dosimetry performed through electron spin resonance (ESR). Here, the authors present the results obtained by ESR measurements of a blend of ammonium tartrate dosemeters and gadolinium oxide (5 % by weight). The choice of low amount of Gd is due to the need of improving neutron sensitivity while not significantly influencing tissue equivalence. A study of the effect of gadolinium presence on tissue equivalence was carried out. The experiments show that the neutron sensitivity is enhanced by more than an order of magnitude even with this small additive content. Monte Carlo simulations on the increment of energy release due to gadolinium presence were carried, and the results were in good agreement with the experimental data.


Electron Spin Resonance Spectroscopy/methods , Gadolinium/radiation effects , Neutrons , Radiometry/methods , Tartrates/radiation effects , Gadolinium/chemistry , Monte Carlo Method , Radiation Dosage , Tartrates/chemistry
17.
Opt Express ; 22(3): 2414-22, 2014 Feb 10.
Article En | MEDLINE | ID: mdl-24663532

Photodynamic therapy for deep-lying lesions needs an appropriate imaging modality, precise evaluation of tissue oxygen and an effective photosensitizer. Gadolinium based metalloporphyrins Gd(III)-HMME is proposed in this study as a potential multifunctional theranostic agent, as photosensitizer, ratiometric oxygen sensor and MRI contrast agent. The time resolved spectroscopy revealed the luminescence peak of Gd(III)-HMME at 710 and 779 nm with a lifetime of 64 µs in oxygen-free methanol to be phosphorescent. This phosphorescence is strongly dependent on dissolved oxygen concentration. Its intensity in oxygen saturated methanol solution is 21% of that in deoxygenated solution. The singlet oxygen quantum yields ΦΔ of HMME and Gd(III)-HMME in air saturated methanol solution were determined to be 0.79 and 0.40 respectively using comparative spectra method. These phenomena indicate that the oxygen sensibility and production of singlet oxygen of Gd(III)-HMME can fulfill the requirement of PDT treatment.


Gadolinium/chemistry , Hematoporphyrins/chemistry , Oxygen/chemistry , Photosensitizing Agents/chemistry , Photosensitizing Agents/radiation effects , Gadolinium/radiation effects , Hematoporphyrins/radiation effects , Light , Luminescent Measurements , Materials Testing , Oxygen/radiation effects , Radiation Dosage , Staining and Labeling
18.
Magn Reson Med ; 72(6): 1746-54, 2014 Dec.
Article En | MEDLINE | ID: mdl-24357240

PURPOSE: Accurate characterization of contrast reagent (CR) longitudinal relaxivity in whole blood is required to predict arterial signal intensity in contrast-enhanced MR angiography (CE-MRA). This study measured the longitudinal relaxation rate constants (R1 ) over a concentration range for non-protein-binding and protein-binding CRs in ex vivo whole blood and plasma at 1.5 and 3.0 Tesla (T) under physiologic arterial conditions. METHODS: Relaxivities of gadoteridol, gadobutrol, gadobenate, and gadofosveset were measured for [CR] from 0 to 18 mM [mmol(CR)/L(blood)]: the latter being the upper limit of what may be expected in CE-MRA. RESULTS: In plasma, the (1) H2 O R1 [CR]-dependence was nonlinear for gadobenate and gadofosveset secondary to CR interactions with the serum macromolecule albumin, and was well described by an analytical expression for effective 1:1 binding stoichiometry. In whole blood, the (1) H2 O R1 [CR]-dependence was markedly non-linear for all CRs, and was well-predicted by an expression for equilibrium exchange of water molecules between plasma and intracellular spaces using a priori parameter values only. CONCLUSION: In whole blood, (1) H2 O R1 exhibits a nonlinear relationship with [CR] over 0 to 18 mM CR. The nonlinearity is well described by exchange of water between erythrocyte and plasma compartments, and is particularly evident for high relaxivity CRs.


Blood Chemical Analysis/methods , Blood Proteins/chemistry , Cell Membrane/chemistry , Contrast Media/chemistry , Gadolinium/chemistry , Magnetic Resonance Imaging/methods , Water/chemistry , Blood Proteins/radiation effects , Contrast Media/radiation effects , Electric Impedance , Gadolinium/radiation effects , Humans , Magnetic Fields , Protons , Radiation Dosage
19.
Radiología (Madr., Ed. impr.) ; 55(5): 398-407, sept. 2013.
Article Es | IBECS | ID: ibc-115436

Objetivos. Evaluar qué porcentaje de hernias de disco desaparece tras un año de seguimiento y a qué ritmo; valorar si el uso del realce con gadolinio en RM tiene valor predictivo de la desaparición de la hernia; y estudiar si el patrón del realce ayuda a predecir la desaparición del fragmento. Material y métodos. Se incluyeron en este estudio prospectivo 118 pacientes con clínica de lumbociática aguda y que presentaban una hernia de disco diagnosticada mediante TC. A 72 pacientes se les realizó una RM con gadolinio cada 6 meses hasta el año o hasta que la hernia de disco desaparecía, y se relacionó la presencia de protrusión, extrusión y el patrón de realce con la desaparición o persistencia del material discal. Se realizó un estudio estadístico univariable y multivariable. Resultados. Un 59% de las hernias de disco desaparecieron tras un año de seguimiento, y de ellas el 66% lo hicieron en los primeros 8 meses. Un 83% de las hernias extruidas desaparecieron, y este dato tiene significación estadística en el análisis multivariable (p < 0,005). La ausencia de realce tiene asociación con la persistencia de la hernia, con significación estadística en el análisis univariable. El patrón de realce no ayuda a predecir la desaparición de la hernia. Hubo 5 hernias que desaparecieron muy pronto, dentro de los primeros 2 meses. Conclusiones. Un alto porcentaje de hernias de disco desaparecen, se ha encontrado la asociación estadísticamente significativa entre extrusión y desaparición, y falta de correlación entre el patrón de captación de gadolinio y la desaparición de la hernia(AU)


Objectives. To evaluate the percentage of disc hernias that have disappeared after one year of follow-up and the time to disappearance. To determine whether gadolinium enhancement is useful for predicting whether the hernia will disappear. To analyze whether the pattern of enhancement can help predict whether the fragment will disappear. Material and methods. This prospective study included 118 patients with acute symptoms of lumbosciatica and a herniated disc diagnosed by CT. In 72 patients, we performed gadolinium-enhanced MRI every 6 months for one year or until the herniation disappeared; we related the findings of protrusion, extrusion, and the enhancement pattern with the disappearance or persistence of herniated disc material. We analyzed the results with univariate and multivariate statistics. Results. The 59% of the hernias disappeared within 1 year of follow-up and 66% disappeared within the first 8 months of follow-up. The 83% of the extruded hernias disappeared, and this was significant in the multivariate analysis (P<.005). The absence of enhancement was significantly associated with the persistence of the hernia in the univariate analysis. The enhancement pattern was not useful for predicting whether the hernia would disappear. Five hernias disappeared within the first two months. Conclusions. A high percentage of disc hernias disappear. We found a significant association between extrusion and disappearance but no correlation between the pattern of gadolinium uptake and the disappearance of the herni(AU)


Humans , Male , Female , Natural History of Diseases , Hernia , Gadolinium , Gadolinium/radiation effects , Prognosis , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy , Lumbosacral Region/pathology , Lumbosacral Region , Prospective Studies , Multivariate Analysis , Odds Ratio , Confidence Intervals , Retrospective Studies
20.
J Nanosci Nanotechnol ; 13(5): 3455-8, 2013 May.
Article En | MEDLINE | ID: mdl-23858878

Medical radiation imaging systems employ phosphors such as CaWO4 as X-ray receptor materials. Unfortunately, the conversion efficiencies of these materials are rather low (approx. 5%). Alternatives that comprise a bulk structure have been fabricated from rare earth metals, but they are not efficient enough to produce high quality images. Nano-phosphors do not suffer from the limitations inherent to the bulk structures of conventional phosphors. We examined the effects of sensitizer doping conditions on the optical characteristics and morphology of the rare earth phosphor Gd2O3:Eu to fabricate a novel type of nano-phosphor. We optimized a temperature solution-combustion procedure for producing phosphors doped with 5 wt% Eu. Scanning electron microscopy images showed that the phosphors were 20-30 nm in diameter and X-ray diffraction analysis revealed that they underwent polycrystalline growth upon the addition of a sensitizer, similar to the polycrystalline growth of bulk phosphors. In addition, the phosphors exhibited a strong peak at 613 nm and luminescence similar to conventional phosphors. Phosphors that were produced using citric acid as a sensitizer showed more than double the level of luminescence and could be used to produce higher quality images compared to non-sensitized phosphors. The phosphors also exhibited a high degree of luminescence stability.


Gadolinium/chemistry , Gadolinium/radiation effects , Luminescent Measurements/methods , Nanostructures/chemistry , Nanostructures/radiation effects , Radiography/methods , Materials Testing , Nanostructures/ultrastructure , Particle Size , X-Rays
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