Gold nanoparticles have been conceived as a radiosensitizer in cancer radiation therapy, but one of the important questions for primary drug screening is what size of gold nanoparticles can optimally enhance radiation effects. Herein, we perform in vitro and in vivo radiosensitization studies of 4.8, 12.1, 27.3, and 46.6 nm PEG-coated gold nanoparticles. In vitro results show that all sizes of the PEG-coated gold nanoparticles can cause a significant decrease in cancer cell survival after gamma radiation. 12.1 and 27.3 nm PEG-coated gold nanoparticles have dispersive distributions in the cells and stronger sensitization effects than 4.8 and 46.6 nm particles by both cell apoptosis and necrosis. Further, in vivo results also show all sizes of the PEG-coated gold nanoparticles can significantly decrease tumor volume and weight after 5 Gy radiations, and 12.1 and 27.3 nm PEG-coated gold nanoparticles have greater sensitization effects than 4.8 and 46.6 nm particles, which can lead to almost complete disappearance of the tumor. In vivo biodistribution confirms that 12.1 and 27.3 nm PEG-coated gold nanoparticles are accumulated in the tumor with high concentrations. The pathology, immune response, and blood biochemistry indicate that the PEG-coated gold nanoparticles have not caused spleen and kidney damages, but give rise to liver damage and gold accumulation. It can be concluded that 12.1 and 27.3 nm PEG-coated gold nanoparticles show high radiosensitivity, and these results have an important indication for possible radiotherapy and drug delivery.

Gold nanoparticles have shown great prospective in cancer diagnosis and therapy, but they can not be metabolized and prefer to accumulate in liver and spleen due to their large size. The gold nanoclusters with small size can penetrate kidney tissue and have promise to decrease in vivo toxicity by renal clearance. In this work, we explore the in vivo renal clearance, biodistribution, and toxicity responses of the BSA- and GSH-protected gold nanoclusters for 24 h and 28 days. The BSA-protected gold nanoclusters have low-efficient renal clearance and only 1% of gold can be cleared, but the GSH-protected gold nanoclusters have high-efficient renal clearance and 36% of gold can be cleared after 24 h. The biodistribution further reveals that 94% of gold can be metabolized for the GSH-protected nanoclusters, but only less than 5% of gold can be metabolized for the BSA-protected nanoclusters after 28 days. Both of the GSH- and BSA-protected gold nanoclusters cause acute infection, inflammation, and kidney function damage after 24 h, but these toxicity responses for the GSH-protected gold nanoclusters can be eliminated after 28 days. Immune system can also be affected by the two kinds of gold nanoclusters, but the immune response for the GSH-protected gold nanoclusters can also be recovered after 28 days. These findings show that the GSH-protected gold nanoclusters have small size and can be metabolized by renal clearance and thus the toxicity can be significantly decreased. The BSA-protected gold nanoclusters, however, can form large compounds and further accumulate in liver and spleen which can cause irreparable toxicity response. Therefore, the GSH-protected gold nanoclusters have great potential for in vivo imaging and therapy, and the BSA-protected gold nanoclusters can be used as the agent of liver cancer therapy.

Non-centrosomal microtubule arrays assemble in differentiated tissues to perform mechanical and transport-based functions. In this study, we identify Caenorhabditis elegans NOCA-1 as a protein with homology to vertebrate ninein. NOCA-1 contributes to the assembly of non-centrosomal microtubule arrays in multiple tissues. In the larval epidermis, NOCA-1 functions redundantly with the minus end protection factor Patronin/PTRN-1 to assemble a circumferential microtubule array essential for worm growth and morphogenesis. Controlled degradation of a γ-tubulin complex subunit in this tissue revealed that γ-tubulin acts with NOCA-1 in parallel to Patronin/PTRN-1. In the germline, NOCA-1 and γ-tubulin co-localize at the cell surface, and inhibiting either leads to a microtubule assembly defect. γ-tubulin targets independently of NOCA-1, but NOCA-1 targeting requires γ-tubulin when a non-essential putatively palmitoylated cysteine is mutated. These results show that NOCA-1 acts with γ-tubulin to assemble non-centrosomal arrays in multiple tissues and highlight functional overlap between the ninein and Patronin protein families.DOI: http://dx.doi.org/10.7554/eLife.08649.001

Gold nanoparticles have potential applications in biomedicine, but one of the important concerns is about their safety. Most toxicology data are derived from in vitro studies and may not reflect in vivo responses. Here, an animal toxicity study of 13.5 nm gold nanoparticles in mice is presented. Animal survival, weight, hematology, morphology, and organ index are characterized at different concentrations (137.5-2200 µg/kg) over 14-28 days. The results show that low concentrations of gold nanoparticles do not cause an obvious decrease in body weight or appreciable toxicity, even after their breakdown in vivo. High concentrations of gold nanoparticles induced decreases in body weight, red blood cells, and hematocrit. It was also found that gold nanoparticles administered orally caused significant decreases in body weight, spleen index, and red blood cells. Of the three administration routes, the oral and intraperitoneal routes showed the highest toxicity, and the tail vein injection showed the lowest toxicity. Combining the results of all of these studies, we suggest that targeted gold nanopartices by tail vein injection may be suitable for enhancement of radiotherapy, photothermal therapy, and related medical diagnostic procedures.