Coated Gadolinium Oxide Research Articles

Biocompatibility and potential anticancer activity of gadolinium oxide (Gd2O3) nanoparticles against nasal squamous cell carcinoma

Chemotherapy as a cornerstone of cancer treatment is slowly being edged aside owing to its severe side effects and systemic toxicity. In this case, nanomedicine has emerged as an effective tool to address these drawbacks. Herein, a biocompatible carrier based on bovine serum albumin (BSA) coated gadolinium oxide nanoparticles (Gd2O3@BSA) was fabricated for curcumin (CUR) delivery and its physicochemical features along with its potential anticancer activity against nasal squamous cell carcinoma were also investigated. It was found that the fabricated Gd2O3@BSA containing CUR (Gd2O3@BSA-CUR) had spherical morphology with hydrodynamic size of nearly 26 nm, zeta-potential of -36 mV and high drug (CUR) loading capacity. Drug release profile disclosed that the release of CUR from the prepared Gd2O3@BSA-CUR nanoparticles occurred in a sustained- and pH-dependent manner. Also, in vitro cytotoxicity analysis revealed that the fabricated Gd2O3@BSA nanoparticles possessed excellent biosafety toward HFF2 normal cells, while Gd2O3@BSA-CUR appeared to display the greatest anticancer potential against RPMI 2650 and CNE-1 cancer cell lines. The results also show that the Gd2O3@BSA nanoparticles were compatible with the blood cells with minor hemolytic effect (< 3%). The manufactured NPs were found to be completely safe for biological applications in an in vivo subacute toxicity study. Taken together, these finding substantiate the potential anticancer activity of Gd2O3@BSA-CUR nanoparticles against nasal squamous cell carcinoma, but the results obtained demand further studies to assess their full potential.

Synthesis and characterization of PVP coated gadolinium oxide nanoparticles for imaging applications

In this work, we present the synthesis and applications of Gd2O3@PVP nanoparticles as an efficient contrast agent for MRI and CT techniques. Gd2O3@PVP nanoparticles have been successfully synthesized by the polyol method using ethylene glycol and poly(vinylpyrrolidone) as solvent and surfactant, respectively. The structure, morphology and characteristic properties of the materials are thoroughly investigated by SEM, TEM, UV-Vis, XRD, FTIR and DLS measurements. As an important result, NPs synthesized under optimized conditions have a diameter in the range of 12 nm and exhibit a good contrast signal in magnetic resonance imaging and computed tomography at relatively low concentration ([NPs] = 0.1 mM for MRI and 1.25 mg.mL-1 for CT). In particular, the concentration of Gd2O3@PVP nanoparticles used in CT is 10 times lower than that of the commercial Iobitridol product (i.e., 12.5 mg.mL-1) to achieve similar signal intensity. This result has an important implication for reducing the dose of contrast agent introduced into the body. The obtained results suggest that PVP-coated Gd2O3 nanoparticles can be applied as multifunctional contrast agents for imaging diagnostic applications in the near future.

Effect of Neodymium Doping on MRI Relaxivity of Gadolinium Oxide Nanoparticles.

Background: Gadolinium oxide nanoparticles as positive contrast material of magnetic resonance imaging (MRI) have attracted a great attention due to the appropriate magnetic properties. One of the most desirable features of these nanoparticles is their ability of doping with other lanthanides which can change their properties.Objective: This study aimed to investigate the effect of neodymium doping on MRI relaxivity of the gadolinium oxide nanoparticles.Material and Methods: In this experimental study, the oleic acid coated gadolinium oxide nanoparticles and the neodymium doped nanoparticles were prepared by polymer pyrolysis method. X-ray diffraction test and scanning electron microscopy were used for characterization of the particles. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to investigate the in vitro cell toxicity of the nanoparticles. The r1 and r2 relaxivities were extracted from the T1 and T2 weighted MR images, respectively.Results: The average size of the cytocompatible spherical-like shape nanoparticles was 40 nm. The neodymium doped nanoparticles produced a significant decrease in the r1 relaxivity, and a 1.7 fold increase in the r2 relaxivity compared to the gadolinium oxide nanoparticles. Conclusion: Doping of neodymium into the gadolinium oxide nanoparticles suppresses the r1 relaxivity and enhances the r2 relaxivity of the nanoparticles.

In vitro and ex vivo relaxometric properties of ethylene glycol coated gadolinium oxide nanoparticles for potential use as contrast agents in magnetic resonance imaging

Magnetic nanoparticles (MNPs) have widely demonstrated their applicability in many biomedical applications including magnetic resonance imaging (MRI), hyperthermia, and drug delivery. However, the effectiveness of MNPs can be limited for in vivo applications due to their hydrophobic surfaces leading to nanoparticle agglomeration and thus requires appropriate surface modification to enhance colloidal stability. Glycols are widely used coating material for surface modifications of MNPs to improve their physicochemical properties and biocompatibility. The present work reports the preparation of two different sized ethylene glycol coated gadolinium oxide nanoparticles (EG@Gd2O3 NPs) using two different synthesis approaches and their applicability as contrast agents in MRI. Thermo-gravimetric analysis and Fourier transform infrared spectroscopy confirmed the successful coating of ethylene glycol on the surface of NPs. We found that independent of the size of NPs, the globular shaped EG@Gd2O3 NPs exhibited similar crystal structures, magnetic properties, and cellular cytotoxicity behavior. However, a significant impact of size on MRI contrast enhancement properties was seen. It was revealed that the relaxivity of EG@Gd2O3 NPs increases with a decrease in particle size. Small sized EG@Gd2O3 NPs (∼12 nm) exhibited a high specific in vitro and ex vivo longitudinal relaxivity of 3.7 and 1.5 mM−1 s−1, respectively, thus clearly elucidating the potential of these NPs for use as local contrast enhancement agents. The present study gives insights into the intrinsic dependence of magnetic resonance contrast effects of NPs on particle size and surface coating layer mass ratio and thus demonstrates the development of efficient magnetic nanoparticles based contrast agents by fine tuning of particle size and surface properties.

Ultrasonication Mediated Fabrication of Glycine Coated Gadolinium Oxide Nanoparticles as MRI Contrast Agents

Gadolinium oxide nanoparticles (Gd2O3NPs) have recently gained significant interest because of their broad range of applications in biomedicine. Nevertheless, their functionality with amino acids was not clearly described. In the current study, the capability of sonication method in the Gd2O3NPs synthesis was explored for the first time. The process of sonication is a very effective technique for fabricating nanoparticles (NPs) which can uniformly disperse in liquids and hence this report describes the utilization of ultra-sonication method for the synthesis of uniform sized (25 nm) Gd2O3NPs coated with Glycine. Fourier transform- Infrared (FT-IR) spectroscopy and dynamic light scattering (DLS) studies were used for confirming the evaluation of Glycine conjugation with NPs. Plasma stability studies clearly showed that, as the time period of incubation increases, the hydrodynamic diameter of NPs in Glycine-Gd2O3 raises slightly to 40 ± 13 nm from 35.24 ± 1.6 nm in the initial stage. Furthermore, the relaxation time, T1 at various time points (1, 2, 4, 6, 9 and 24 h) during the incubation was determined and these values confirmed the excellent stability of Glycine-Gd2O3NPs MRI signal present in plasma.

Synthesis, MR Relaxivities, and In Vitro Cytotoxicity of 3,5-Diiodo-L-tyrosine-Coated Gd2O3 Nanoparticles

In this study, we report the synthesis and characterization of 3,5-Diiodo-L-tyrosine (DLT)-coated gadolinium oxide (Gd2O3) nanoparticles. The bonding status of DLT-coated Gd2O3 nanoparticles (DLT-NPs) were confirmed by Fourier transform infrared (FT-IR) absorption spectra and thermogravimetric analysis (TGA). The surface coating amount was estimated to be 73% in weight percent from a TGA. High-resolution transmission electron microscope (HR-TEM) shows that DLT-NPs were spherical in shape with an average diameter 2 nm. The MR relaxivity measurements confirmed that the DLT-NPs have higher r1 = 9.24 s-1 mM-1 than commercially available contrast agents. Furthermore, the bio-compatibility of the DLT-NPs were measured by cytotoxicity test, which has demonstrated that the cell viability reached up to 60% with Gd concentrations up to 50 μM for both DU145 and NCTC1469 cell lines, making them a promising candidate for biomedical applications.

Ultrasonication assisted fabrication of l-lysine functionalized gadolinium oxide nanoparticles and its biological acceptability

Gadolinium oxide nanoparticles (GdO) have recently gained attention due to their diverse bio-applications. However, their functionalization with amino acids has not been reported yet to the best of our knowledge. In the present report, the potential of sonication technique (for the first time to the best of our knowledge) in the fabrication of GdO nanoparticles was explored. Sonication is an efficient technique for the synthesis of evenly dispersing nanoparticles in liquids thus, the present report highlights the use of ultrasonication technique for the fabrication of uniform 2 nm sized luminescent l-lysine coated gadolinium oxide nanoparticles (l-lysine@GdO). Investigation of l-lysine conjugation with nanoparticles was confirmed by FT-IR, Differential Scanning Calorimetric analysis and Zeta potential. The interactions of serum protein (BSA) with synthesized nanoparticles have been explored using UV–visible spectroscopy, Fluorescence spectroscopy and Circular Dichroism (CD). The synthesized l-lysine coated nanoparticles demonstrated potential for antimicrobial and antifungal agents, which has been tested against two bacterial strains Escherichia coli and Staphylococcus aureus and two antifungal Candida albicans and Candida glabrata cells. The minimal inhibition concentrations (MIC) of nanoparticles against E.coli and S. aureus are 8 µg mL−1 and 16 µg mL−1, respectively. The cell viability, MTT assay on HaCaT cell lines revealed the non-toxicity of synthesized nanoparticles.

Biocompatible gadolinium oxide nanoparticles as efficient agent against pathogenic bacteria

The inappropriate and surfeit use of antibiotics have generated a hunt for safe and alternative antimicrobial agents against pathogenic bacteria. With the advancement in nanoscience and nanotechnology, promising opportunities for examining the bacterial effect of metal nanoparticles were demonstrated in literature. Focusing on this, our present study presentssynthesis of l-ascorbic coated gadolinium oxide nanoparticles via a simple precipitation route. Their complete characterization and detailed stability studies were carried out. The obtained nanoparticles were characterized by Fourier transform infrared (FT-IR) spectroscopy, confirming that l-ascorbic acid onto the surface of nanoparticles. The size and morphology were analyzed by Transmission electron Microcopy (TEM) and Field emission scanning electron microscopy (FE-SEM) which reveals their spherical nature. The stability studies were performed to know about their chemical and colloidal stability. The synthesized nanoparticles were found to be non-toxic to HaCaT cells upto the concentration of 125 µg/mL. The antimicrobial effect of nanoparticles was analyzed against three bacterial strains; E. coli, S. aureus and S. typhimurium. To summarize, the synthesized nanoparticles are found to be safe and protective against pathogenic bacteria. They further can be explored in biomedical applications considering their non-toxic nature.

Rose Bengal attached and dextran coated gadolinium oxide nanoparticles for potential diagnostic imaging applications

We report here, reverse micelle mediated synthesis of multifunctional dextran (dex) coated Gd2O3 nanoparticles (NPs) carrying rose bengal (RB) dye for magnetic resonance and optical imaging. The diameter of these RB attached dex coated Gd2O3 NPs (Gd-dex-RB NPs) was found to be ~17 nm as measured by TEM. NMR line broadening effect on the surrounding water protons affirmed the paramagnetic nature of these NPs. Optical properties of Gd-dex-RB NPs were validated by UV‐Vis and fluorescence spectroscopy. Time dependent release profile of RB from NPs at two different pH of 7.4 and 5.0 revealed that these NPs behave as slow releasing system. In-vitro study revealed that NPs are efficiently taken up by cells and show optical activity in cellular environment. In vitro cell viability (SRB) assay was performed on cancerous (A-549, U-87) and normal (HEK-293) cell lines, showed the absence of cytotoxic effect of Gd-dex-RB NPs. Therefore, such multifunctional NPs can be efficiently used for bio-imaging and optical tracking.

FITC-Dextran entrapped and silica coated gadolinium oxide nanoparticles for synchronous optical and magnetic resonance imaging applications

We report, microemulsion mediated synthesis of FITC-dextran dye entrapped and silica coated Gd2O3 nanoparticles (NPs) for dual purpose of optical and magnetic resonance imaging, in the present study. TEM image revealed that the average size of the NPs is 18nm and hydrodynamic diameter of the particles as measured by DLS comes out to be about 16nm. Gd2O3 core show paramagnetism which is affirmed by the NMR line broadening effect on neighboring water proton spectrum and also by magnetization curve obtained in VSM analysis. The fluorescence of the entrapped dye is confirmed by the UV–vis and fluorescence spectroscopy. Nanoencapsulation of FITC-dextran fluorophore was found to increase its optical activity and provided a blanket against quenching. Moreover, TGA data revealed that entrapment of dye imparts thermal stability to it and enhances its fluorescence in comparison to bare dye. The release kinetic pattern (at pH 7.4) of the entrapped dye revealed that these particles behave as non-releasing system. The in-vitro cell viability (SRB) assay of the particles done on normal cell line (HEK-293) as well as cancerous cell line (A-549) indicated non-cytotoxic nature of the particles. In a nut-shell, these particles have the potential to be efficiently used for optical and magnetic resonance imaging. We anticipate that further optimization of these particles can be done by either conjugating or entrapping a drug for targeted drug delivery which would open more prospective options in biomedical field.

양성자 빔 암치료효과 개선을 위한 산화철 및 산화가돌리늄 나노입자 기반의 방사선증감제 합성

Metallic nanoparticles have attractive properties in biomedical applications such as diagnostics and therapeutics. Cross linked dextran coated iron oxide nanoparticles (SPIONs) and silica coated gadolinium oxide nanoparticles (SPGONs) have been synthesized as a radiosensitizer in the proton beam cancer therapy. The dextran and silicaused for the protective moieties on the SPIONs and SPGONs respectively. Size distributions of synthesized nanoparticles were confirmed 3~5 nm for SPIONs and 30~100 nm for SPGONs by transmission electron microscope (TEM). Cell survival fraction measurement and Western blot assay were performed to evaluate the radiosensitization effects of synthesized radiosensitizer. The calculated radiosensitization of SPIONs and SPGONs at 90 % cell death from the measured cell survival curves were 1.23 and 1.03 respectively. Western blotting results also show the same consistent results that the amount of released cytochrome c from mitochondria was considerably increased for the cancer cells taken up SPIONs. Keyword : Metallic nanoparticle, Radiosensitizer, Iron oxide nanoparticle, Gadolinium oxide nanoparticle, Cytochrom C, Western blotting

Gadolinium Oxide Nanoparticles as Potential Multimodal Imaging and Therapeutic Agents

Potentials of hydrophilic and biocompatible ligand coated gadolinium oxide nanoparticles as multimodal imaging agents, drug carriers, and therapeutic agents are reviewed. First of all, they can be used as advanced T1 magnetic resonance imaging (MRI) contrast agents because they have r1 larger than those of Gd(III)-chelates due to a high density of Gd(III) per nanoparticle. They can be further functionalized by conjugating other imaging agents such as fluorescent imaging (FI), X-ray computed tomography (CT), positron emission tomography (PET), and single photon emission tomography (SPECT) agents. They can be also useful for drug carriers through morphology modifications. They themselves are also potential CT and ultrasound imaging (USI) contrast and thermal neutron capture therapeutic (NCT) agents, which are superior to commercial iodine compounds, air-filled albumin microspheres, and boron ((10)B) compounds, respectively. They, when conjugated with targeting agents such as antibodies and peptides, will provide enhanced images and be also very useful for diagnosis and therapy of diseases (so called theragnosis).

Optical and rheological study of gamma irradiated rare-earth nanoparticle based ferrofluids

The present work reports on the optical and rheological properties of unexposed and gamma irradiated rare-earth (RE) oxide nanoparticle-based ferrofluids (FF). The ferrofluids were prepared by dispersing surfactant coated gadolinium oxide (Gd2O3) nanoparticles in ethanol medium and later on subjected to energetic gamma irradiation (1.25MeV) at select doses. As predicted from transmission electron microscopy and X-ray diffraction (XRD) studies, the synthesized nanoparticles are of ∼7nm size which crystallize into cubic crystal structure. The photoluminescence response reveals creation of defect states on nanoparticle surfaces when FFs are subjected to gamma irradiation. Whereas, rheology measurements showed unusual shear thinning behavior of the ferrofluids. The flow behavior of all the samples can be correlated to the bi-exponential decay curve fitting which reveals that decay phenomenon is governed by two independent mechanism: fast and slow events. The variation of the decay parameter with irradiation dose is attributed to the creation of point defects and weakening of inter nanoparticle bonding.

Fluorescein-polyethyleneimine coated gadolinium oxide nanoparticles as T1 magnetic resonance imaging (MRI)–cell labeling (CL) dual agents

We report the synthesis, characterization and application of highly water-soluble fluorescein-polyethyleneimine (PEI) coated gadolinium oxide (Gd2O3) nanoparticles to magnetic resonance imaging (MRI) and cell labeling (CL). The average particle diameter and average hydrodynamic diameter were estimated to be 3.92 and 7.5 nm, respectively. Fluorescein-PEI was prepared from EDC/NHS coupling method. The surface coating was characterized by the FT-IR absorption spectrum and the surface coating amount was estimated to be 22.42 wt% from a TGA analysis, corresponding to 0.65 nm−2 grafting density. The fluorescein-PEI coated gadolinium oxide nanoparticles showed r1 and r2 of 6.76 and 20.27 s−1mM−1, respectively, and a strong fluorescence at ∼527 nm. A pronounced positive contrast enhancement was clearly observed in 3 tesla T1 MR images of a rat with a liver tumor after injection of an aqueous sample solution into a rat tail vein. After treatment of DU145 cells with a sample solution, a strong fluorescence in confocal images was also observed. These two results together confirm the excellent MRI-CL dual functionality of fluorescein-PEI coated gadolinium oxide nanoparticles.

Synthesis of gadolinium oxide magnetoliposomes for magnetic resonance imaging

A method for the synthesis of gadolinium oxide magnetoliposomes, i.e., nanosized gadolinium oxide magnetic particles coated by a phospholipid membrane, is presented. Magnetoliposomes were prepared by reacting lauric acid coated gadolinium oxide nanoparticles with dimyristoylphosphatidylcholine liposomes prepared using a direct injection method. The gadolinium oxide magnetoliposomes were characterized using transmission electron microscopy imaging, x-ray diffraction, and fluorescence. The magnetic properties of the magnetoliposomes were investigated with a superconducting quantum interference device magnetometer and nuclear magnetic resonance (NMR) spectrometry. Our results indicate that the magnetoliposomes contain approximately spherical nanoparticles averaging 20 nm in diameter. The occurrence of a phospholipid bilayer surrounding the magnetic particles is confirmed both by transmission electron micrographs of samples negatively stained with uranyl acetate and by digital fluorescence imaging microscopy measurements of magnetoliposomes labeled with fluorescein. The particles are paramagnetic at room temperature. NMR measurements show that the ratio between the relaxivities of the particles depends largely on their preparation.