Gadolinium Oxide Nanocrystals Research Articles

Gadolinium Oxide Nanoparticles Reinforce the Fractionated Radiotherapy-Induced Immune Response in Tri-Negative Breast Cancer via cGAS-STING Pathway.

Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo. 1.0 T small animal MR imaging (MRI) system was employed to trace GONs in vivo, while 225 kVp X-ray irradiation equipment was utilized for investigating the radiosensitization of GONs in 4T1 breast cancer cells in vitro and in vivo. Western blot, quantitative real-time PCR (RT-qPCR), immunohistochemistry, immunofluorescence, clonal survival assay, flow cytometry and reactive oxygen species assay were used to explore the biological mechanism of GON sensitization. GONs exhibited exceptional utility as contrast agents for both in vivo and in vitro MRI imaging. Interestingly, a single dose of 8.0 Gy X-rays together with GONs failed to confer superior therapeutic effects in tumor-bearing mice, while only 3.0 Gy × 3 fractions X-rays combined with GONs exhibited effective tumor growth inhibition. Moreover, fractionated X-ray irradiation with GONs demonstrated a superior capacity to activate the cGAS-STING pathway. Fractionated X-ray irradiation in the presence of GONs has demonstrated the most significant activation of the anti-tumor immune response by boosting the cGAS-STING pathway.

Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy.

BackgroundGadolinium-based nanoparticles (GdNPs) have been used as theranostic sensitizers in clinical radiotherapy studies; however, the biomechanisms underlying the radio-sensitizing effects of GdNPs have yet to be determined. In this study, ultra-small gadolinium oxide nanocrystals (GONs) were employed to investigate their radiosensitizing effects and biological mechanisms in non-small-cell lung cancer (NSCLC) cells under X-ray irradiation.Method and materialsGONs were synthesized using polyol method. Hydroxyl radical production, oxidative stress, and clonogenic survival after X-ray irradiation were used to evaluate the radiosensitizing effects of GONs. DNA double-strand breakage, cell cycle phase, and apoptosis and autophagy incidences were investigated in vitro to determine the radiosensitizing biomechanism of GONs under X-ray irradiation.ResultsGONs induced hydroxyl radical production and oxidative stress in a dose- and concentration-dependent manner in NSCLC cells after X-ray irradiation. The sensitizer enhancement ratios of GONs ranged between 19.3% and 26.3% for the NSCLC cells under investigation with a 10% survival rate compared with that of the cells treated with irradiation alone. Addition of 3-methyladenine to the cell medium decreased the incidence rate of autophagy and increased cell survival, supporting the idea that the GONs promoted cytostatic autophagy in NSCLC cells under X-ray irradiation.ConclusionThis study examined the biological mechanisms underlying the radiosensitizing effects of GONs on NSCLC cells and presented the first evidence for the radiosensitizing effects of GONs via activation of cytostatic autophagy pathway following X-ray irradiation.

In Vivo Microcomputed Tomography of Nanocrystal-Doped Tissue Engineered Scaffolds.

Tissue engineered scaffolds (TES) hold promise for improving the outcome of cell-based therapeutic strategies for a variety of biomedical scenarios, including musculoskeletal injuries, soft tissue repair, and spinal cord injury. Key to TES research and development, and clinical use, is the ability to longitudinally monitor TES location, orientation, integrity, and microstructure following implantation. Here, we describe a strategy for using microcomputed tomography (microCT) to visualize TES following implantation into mice. TES were doped with highly radiopaque gadolinium oxide nanocrystals and were implanted into the hind limbs of mice. Mice underwent serial microCT over 23 weeks. TES were clearly visible over the entire time course. Alginate scaffolds underwent a 20% volume reduction over the first 6 weeks, stabilizing over the next 17 weeks. Agarose scaffold volumes were unchanged. TES attenuation was also unchanged over the entire time course, indicating a lack of nanocrystal dissolution or leakage. Histology at the implant site showed the presence of very mild inflammation, typical for a mild foreign body reaction. Blood work indicated marked elevation in liver enzymes, and hematology measured significant reduction in white blood cell counts. While extrapolation of the X-ray induced effects on hematopoiesis in these mice to humans is not straightforward, clearly this is an area for careful monitoring. Taken together, these data lend strong support that doping TES with radiopaque nanocrystals and performing microCT imaging, represents a possible strategy for enabling serial in vivo monitoring of TES.

Nanocomposites: Smart Albumin‐Biomineralized Nanocomposites for Multimodal Imaging and Photothermal Tumor Ablation (Adv. Mater. 26/2015)

A nanoplatform of cancer-targeted nanocomposites is demonstrated by H. B. Chen and co-workers on page 3874 through the assembly of gadolinium oxide nanocrystals with a protein scaffold in conjugation with near-infrared cyanine dye, directed to trimodal near-infrared fluorescence/photoacoustics/magnetic-resonance imaging with complementary features, including ultrasensitivity, precise anatomical localization, and good spatial resolution, as well as smart photothermal efficacy with tumor ablation.

Smart Albumin-Biomineralized Nanocomposites for Multimodal Imaging and Photothermal Tumor Ablation.

Smart cyanine-grafted gadolinium oxide nanocrystals (Cy-GdNCs) obtained by albumin-based biomineralization are shown to be theranostic nanocomposites, with promising properties for trimodal near-infrared fluorescence/photoacoustics/magnetic-resonance imaging-guided photothermal tumor ablation.

Effects of charge storage dielectric thickness on hybrid gadolinium oxide nanocrystal and charge trapping nonvolatile memory

The characteristics of hybrid gadolinium oxide nanocrystal (Gd2O3-NC) and gadolinium oxide charge trapping (Gd2O3-CT) memories were investigated with different Gd2O3 film thickness. By performing the rapid thermal annealing on Gd2O3 films with different thickness, the Gd2O3-NCs with the diameter of 6–9 nm for charge storage, surrounded by the amorphous Gd2O3 (α-Gd2O3) layer, were formed. The α-Gd2O3 layer was considered to be the charge trapping layer, resulting in the large memory window of Gd2O3-NC/CT memories with thick Gd2O3 film. The charge trapping energy level of the Gd2O3-NCs and α-Gd2O3 layer was extracted to be 0.16 and 0.45 eV respectively by using the temperature-dependent retention measurement. Further, after a 106 program/erase cycling operation, the memory with thin Gd2O3 film can be predicted to sustain a 94% memory window of the first cycling one while the memory with thick Gd2O3 film suffered from a 30% charge loss because of the traps within the α-Gd2O3 layer. The Gd2O3 film thickness of 10 nm was optimized to exhibit superior performances of the Gd2O3-NC/CT memory, which can be applied into the nonvolatile memory.

Biocompatible composite nanoparticles with large longitudinal relaxivity for targeted imaging and early diagnosis of cancer.

Early diagnosis of cancer greatly increases the chances of successful treatment by radical resection. The sensitivity of magnetic resonance imaging (MRI) techniques for detecting early stage tumors can be increased with the assistance of a positive MRI contrast agent. However, the traditional positive MRI contrast agents, such as Gd-chelates and Gd-based inorganic nanoparticles, are often limited by their cytotoxicity and low specificity. Here, we propose a new design of MRI contrast agent based on gadolinium oxide nanocrystals (GON) for targeted imaging and cancer early diagnosis with good biocompatibility. The GON were prepared using a polyol method and then encapsulated into albumin nanoparticles (AN), which were cross-linked with glutaraldehyde and found to exhibit bright and stable autofluorescence without conjugation to any fluorescent agent. After that, a target molecule, folic acid (FA), was conjugated onto the surface of the GON-loaded AN (GON-AN) to construct a GON-AN-FA composite. The as-prepared nanoparticles are biocompatible and stable in serum. The results of MRI relaxation studies show that the longitudinal relaxivities (r1) of GON-AN (11.6 mM-1 s-1) and GON-AN-FA (10.8 mM-1 s-1) are much larger than those of traditional positive MRI contrast agents, such as Magnevist (3.8 mM-1 s-1). The results of cell viability assays indicate that GON-AN and GON-AN-FA are almost non-cytotoxic. Furthermore, the specificities of GON-AN and GON-AN-FA were evaluated with two kinds of cancer cells which overexpress folate receptor alpha (FRα). The results reinforce that the autofluorescent GON-AN-FA is able to target cancer cells via recognition of the ligand FA and the receptor FRα. Therefore, our autofluorescent GON-AN-FA possessing a large longitudinal relaxivity and good biocompatibility represents a significant advance for the targeted imaging and early diagnosis of cancer.

Synthesis of bulk-size transparent gadolinium oxide-polymer nanocomposites for gamma ray spectroscopy.

Heavy element loaded polymer composites have long been proposed to detect high energy X- and γ-rays upon scintillation. The previously reported bulk composite scintillators have achieved limited success because of the diminished light output resulting from fluorescence quenching and opacity. We demonstrate the synthesis of a transparent nanocomposite comprising gadolinium oxide nanocrystals uniformly dispersed in bulk-size samples at a high loading content. The strategy to avoid luminescence quenching and opacity in the nanocomposite was successfully deployed, which led to the radioluminescence light yield of up to 27 000/MeV, about twice as much as standard commercial plastic scintillators. Nanocomposites monoliths (14 mm diameter by 3 mm thickness) with 31 wt% loading of nanocrystals generated a photoelectric peak for Cs-137 gamma (662 keV) with 11.4% energy resolution.

Tunable bandgap energy of fluorinated nanocrystals for flash memory applications produced by low-damage plasma treatment

A plasma system with a complementary filter to shield samples from damage during tetrafluoromethane (CF4) plasma treatment was proposed in order to incorporate fluorine atoms into gadolinium oxide nanocrystals (Gd2O3-NCs) for flash memory applications. X-ray photoelectron spectroscopy confirmed that fluorine atoms were successfully introduced into the Gd2O3-NCs despite the use of a filter in the plasma-enhanced chemical vapour deposition system to shield against several potentially damaging species. The number of incorporated fluorine atoms can be controlled by varying the treatment time. The optimized memory window of the resulting flash memory devices was twice that of devices treated by a filterless system because more fluorine atoms were incorporated into the Gd2O3-NCs film with very little damage. This enlarged the bandgap energy from 5.48 to 6.83 eV, as observed by ultraviolet absorption measurements. This bandgap expansion can provide a large built-in electric field that allows more charges to be stored in the Gd2O3-NCs. The maximum improvement in the retention characteristic was >60%. Because plasma damage during treatment is minimal, maximum fluorination can be achieved. The concept of simply adding a filter to a plasma system to prevent plasma damage exhibits great promise for functionalization or modification of nanomaterials for advanced nanoelectronics while introducing minimal defects.

Microstructural effect of gadolinium oxide nanocrystals upon annealing on electrical properties of memory devices

The microstructure evolution of sputtered gadolinium oxide nanocrystal (NC) memory devices upon annealing has been characterized in detail by transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). TEM results indicate that the as-deposited film is composed of metallic Gd clusters embedded in an amorphous GdxOy matrix. The Gd clusters undergo phase transformation to oxide NCs upon annealing, reaching a maximum density of 7.9–9.1×1011cm−2 at 850°C, which is consistent with the largest memory window width. Upon annealing at even higher temperature, TEM diffraction patterns and XPS composition profiles indicate apparent Si diffusion into the NC layer, probably from the SiO2 tunneling oxide or the Si substrate, leading to the formation of gadolinium silicate NCs. The presence of silicate NCs gradually deteriorates the device performance due to the reduction of barrier confinement for stored charges, although the dot density is only marginally decreased. The results suggest that the optimum memory device performance is dominated by not only the most considered size and density of NCs, but also the composition and phase inside.

Dielectric properties of colloidal Gd2O3 nanocrystal films fabricated via electrophoretic deposition

We investigated the dielectric characteristics of [Al/Gd2O3/Si] metal-oxide-semiconductor (MOS) capacitors, which were fabricated from films of gadolinium oxide (Gd2O3) nanocrystals used as the gate oxide layer. Electrophoretic deposition cast Gd2O3 nanocrystal films of different thicknesses by varying the concentration of the nanocrystal suspensions. Capacitance-voltage (C-V) measurements of the MOS capacitors exhibited hysteresis, which indicated potentially favorable charge-storage properties. The films’ dielectric constant (κ=3.90), calculated from the C-V data, led to the packing density of nanocrystals within the film (66%), which is in the glassy regime approximated by randomly closed packed spheres.

Characteristics of Gadolinium Oxide Nanocrystal Memory with Optimized Rapid Thermal Annealing

Gadolinium oxide nanocrystal (Gd 2 O 3 -NC) memories treated by postdeposition rapid thermal annealing were investigated. Bandgap offset performed by a crystallized Gd 2 O 3 -NC dot surrounded by amorphous Gd 2 O 3 dielectrics is successfully demonstrated and proven by the transmission electron microscopy images and electron diffraction pattern. The Gd 2 O 3 -NC memory exhibits a hysteresis memory window of 4 V and NC dot density of more than 8.5 X 10 11 cm -2 . In addition, the formation of Gd 2 O 3 -NC and charge loss characteristics on annealing temperature were analyzed and optimized at 850°C. The data endurance of 10 4 program and erase cycling for a sufficient memory window (>2 V) was also observed for the Gd 2 O 3 nanocrystal memory.