Harnessing Nuclear Energy to Gold Nanoparticles for the Concurrent Chemoradiotherapy of Glioblastoma.

Nuclear fission reactions can release massive amounts of energy accompanied by neutrons and γ photons, which create a mixed radiation field and enable a series of reactions in nuclear reactors. This study demonstrates a one-pot/one-step approach to synthesizing radioactive gold nanoparticles (RGNP) without using radioactive precursors and reducing agents. Trivalent gold ions are reduced into gold nanoparticles (8.6-146 nm), and a particular portion of 197Au atoms is simultaneously converted to 198Au atoms, rendering the nanoparticles radioactive. We suggest that harnessing nuclear energy to gold nanoparticles is feasible in the interests of advancing nanotechnology for cancer therapy. A combination of RGNP applied through convection-enhanced delivery (CED) and temozolomide (TMZ) through oral administration demonstrates the synergistic effect in treating glioblastoma-bearing mice. The mean survival for RGNP/TMZ treatment was 68.9 ± 9.7 days compared to that for standalone RGNP (38.4 ± 2.2 days) or TMZ (42.8 ± 2.5 days) therapies. Based on the verification of bioluminescence images, positron emission tomography, and immunohistochemistry inspection, the combination treatment can inhibit the proliferation of glioblastoma, highlighting the niche of concurrent chemoradiotherapy (CCRT) attributed to RGNP and TMZ.

NeuTHOR Station-A Novel Integrated Platform for Monitoring BNCT Clinical Treatment, Animal and Cell Irradiation Study at THOR.

(1) Background: A well-established Boron Neutron Capture Therapy (BNCT) facility includes many essential systems, which are the epithermal neutron beam system, on-line monitoring system (OMS), QA/QC (quality assurance or quality control) system, boron concentration (BC) measurement system, and treatment planning system (TPS). Accurate data transmission, monitoring, and deposition among these systems are of vital importance before, during, and after clinical, animal, and cell BNCT irradiation. This work developed a novel integrated platform NeuTHOR Station (NeuTHORS) for BNCT at Tsing Hua Open-pool Reactor (THOR). Apart from the data of the OMS and QA/QC system, the data of BC and TPS can be loaded on NeuTHORS before BNCT clinical, animal, and cell irradiation. (2) Methods: A multi-paradigm computer programming language c# (c sharp) was used to develop the integrated platform NeuTHORS. The design of NeuTHORS is based on the standard procedures of BNCT treatment or experiment at THOR. Moreover, parallel testing with OMS-BNCT (the former OMS) and QA/QC of THOR was also performed for more than 70 times to verify the validation of NeuTHORS. (3) Results: According to the comparisons of the output, NeuTHORS and OMS-BNCT and QA/QC of THOR show very good consistency. NeuTHORS is now installed on an industrial PC (IPC) and successfully performs the monitoring of BNCT Treatment at THOR. Patients' f BC and TPS data are also input into NeuTHORS and stored on IPC through an internal network from BC measurement room and TPS physicist. Therefore, the treatment data of each patient can be instantaneously established after each BNCT treatment for further study on BNCT. NeuTHORS can also be applied on data acquisition for a BNCT-related study, especially for animal or cell irradiation experiments. (4) Conclusions: A novel integrated platform NeuTHOR Station for monitoring BNCT clinical treatment and animal and cell irradiation study has been successfully established at THOR. With this platform, BNCT radiobiology investigations will be efficiently performed and a thorough data storage and analysis system of BNCT treatments or experiments can thus be systematically built up for the further investigation of BNCT at THOR.

[Temporal and spatial changes of urban impervious surface and its influence on urban ecolo-gical quality: A comparison between Shanghai and New York]. / ä¸Šæµ·å’Œçº½çº¦åŸŽå¸‚ä¸é€æ°´é¢æ—¶ç©ºå˜åŒ–åŠå ¶å¯¹ç”Ÿæ€è´¨é‡å½±å“çš„å¯¹æ¯”.

The urban spatial expansion has led to the considerable substitution of natural vegetation-dominated land surfaces by impervious surfaces, especially in large cities, with great impacts on urban ecological quality. Two most heavily populated cities, Shanghai of China and New York of USA, were chosen as the study cases. Based on Landsat images obtained in 1989, 2002, 2015 in Shanghai and in 1991, 2001, 2015 in New York, normalized difference impervious surface index (NDISI) was used to extract impervious surface (IS) information. The remote sensing based ecolo-gical index (RSEI) was then applied to evaluate the changes of urban ecological quality caused by the increased impervious surface. Furthermore, landscape pattern indices were used to analyze the differences of spatial structure of impervious surface between Shanghai and New York and their influences on urban ecological quality. The results showed a significant difference in urban expansion rate and pattern between Shanghai and New York from the early 1990s to 2015. The IS expansion area in Shanghai was 17.4 times as much as that in New York. The annual IS increase rate of Shanghai was 62.2 times as much as that of New York. Shanghai had experienced an expansion from urban center to the surrounding countryside in a concentric ring pattern, whereas New York showed no much expansion but had IS increase mainly within the inner city through space filling pattern. These differences in IS change rate and spatial distribution pattern had resulted in the difference in urban ecological quality of the two cities. The mean RSEI in Shanghai dropped from 0.717 in 1989 to 0.453 in 2015, with a decrease of 36.8%. In contrast, the RSEI of New York had a decline of 6.9% from 0.552 in 1991 to 0.514 in 2015. The poor ecological condition urban area tended to have large IS patches that were well connected and aggregated.

Establishment of a trimodality analytical platform for tracing, imaging and quantification of gold nanoparticles in animals by radiotracer techniques.

This study aims to establish a (198)Au-radiotracer technique for in vivo tracing, rapid quantification, and ex vivo visualization of PEGylated gold nanoparticles (GNPs) in animals, organs and tissue dissections. The advantages of GNPs lie in its superior optical property, biocompatibility and versatile conjugation chemistry, which are promising to develop diagnostic probes and drug delivery systems. (198)Au is used as a radiotracer because it simultaneously emits beta and gamma radiations with proper energy and half-life; therefore, (198)Au can be used for bioanalytical purposes. The (198)Au-tagged radioactive gold nanoparticles ((198)Au-GNPs) were prepared simply by irradiating the GNPs in a nuclear reactor through the (197)Au(n,γ)(198)Au reaction and subsequently the (198)Au-GNPs were subjected to surface modification with polyethylene glycol to form PEGylated (198)Au-GNPs. The (198)Au-GNPs retained physicochemical properties that were the same as those of GNP before neutron irradiation. Pharmacokinetic and biodisposition studies were performed by intravenously injecting three types of (198)Au-GNPs with or without PEGylation into mice; the γ radiation in blood specimens and dissected organs was then measured. The (198)Au-radiotracer technique enables rapid quantification freed from tedious sample preparation and shows more than 95% recovery of injected GNPs. Clinical gamma scintigraphy was proved feasible to explore spatial- and temporal-resolved biodisposition of (198)Au-GNPs in living animals. Moreover, autoradiography, which recorded beta particles from (198)Au, enabled visualizing the heterogeneous biodisposition of (198)Au-GNPs in different microenvironments and tissues. In this study, the (198)Au-radiotracer technique facilitated creating a trimodality analytical platform for tracing, quantifying and imaging GNPs in animals.

Kinetics and tissue distribution of neutron-activated zinc oxide nanoparticles and zinc nitrate in mice: effects of size and particulate nature.

Although zinc oxide nanoparticles (ZnONPs) have been applied in nanotechnology, their kinetics and tissue distribution in vivo are unknown. Here we compared the kinetics and tissue distribution of 10 nm (65)ZnONPs, 71 nm (65)ZnONPs and (65)Zn(NO(3))(2) in mice after intravenous injection. The areas under the curves and the half-lives in the second compartment of (65)Zn(NO(3))(2) were greater than those of (65)ZnONPs; the kinetic parameters were similar for both (65)ZnONPs. However, the tissue distributions for the three forms were different. ZnONPs preferentially accumulated in the liver and spleen at 24 h. At day 28, (65)Zn concentration was highest in bone and the proportion of recovered (65)Zn radioactivity was highest in the carcass; these had the same ranking, 10 nm (65)ZnONPs > 71 nm (65)ZnONPs>  (65)Zn(NO(3))(2). Although more than 80% of the 10 nm (65)ZnONPs had been excreted by day 28, greater amounts of the 10 nm (65)ZnONPs than the 71 nm (65)ZnONPs or (65)Zn(NO(3))(2) had accumulated in other organs (brain, lung, heart and kidneys). Zn ions seem to have a longer half-life in the plasma, but ZnONPs show greater tissue accumulation. Although the size of the ZnONPs had no obvious effect on the kinetics, nevertheless the smaller ZnONPs tended to accumulate preferentially in some organs.

The use of radioactive zinc oxide nanoparticles in determination of their tissue concentrations following intravenous administration in mice.

The increasing uses of zinc oxide nanoparticles (ZnONPs) in coatings, paints, personal care products and many other products increase the possibility of the body's exposure to ZnONPs. Accurate and quantitative profiling on the tissue distribution and body clearance of ZnONPs, which is an important factor to clarify the acute and chronic safety concerns of ZnONPs, is interfered by the abundance of the body's endogenous zinc moiety. In this report, radioactive zinc oxide nanoparticles (R-ZnONPs) generated from neutron activation were employed for the in vivo bio-distribution studies using mice as the animal model. Gamma-ray emitting radioactive R-ZnONPs were produced from neutron activation. Zeta potentials of the ZnONPs before and after the neutron irradiation remained about the same, and R-ZnONPs largely remained its original nano-particulate form after neutron irradiation. After intravenous administration into ICR mice, R-ZnONPs exhibited a primary retention in lung (43.6% injected dose (ID)/g tissue wet weight) for the first hour and began to be translocated to intestinal tract for feces excretion at a later stage. This type of labeling free and radioactive nanoparticles retains the surface property and can be a convenient protocol for studying bio-distribution of nanoparticles in pristine chemical form.