Significance: Copper-cysteamine nanoparticles can be activated directly by X-rays to produce singlet oxygen. The use of copper-cysteamine nanoparticles (conjugated with pH-low insertion peptide) can enhance the effects of X-ray–induced photodynamic therapy, to lead to improved tumor treatment in mice. The results of this study demonstrate the potential of copper-cysteamine nanoparticles with deeply penetrating X-rays in the treatment of mammalian cancer to overcome current limitations of low penetration, light-induced photodynamic therapy treatment that can only treat superficial cancers.

The Copper-cysteamine (Cu-Cy) nanoparticle is a novel sensitizer with a potential to increase the effectiveness of radiation therapy for cancer treatment. In this work, the effect of nanoparticle size and the energy of X-rays on the effectiveness of radiation therapy are investigated. The effect of the particle size on their performance is very complicated. The nanoparticles with an average size of 300 nm have the most intense photoluminescence, the nanoparticles with the average size of 100 nm have the most reactive oxygen species production upon X-ray irradiation, while the nanoparticles with the average size of 40 nm have the best outcome in the tumor suppression in mice upon X-ray irradiation. For energy, 90 kVp radiation resulted in smaller tumor sizes than 250 kVp or 350 kVp radiation energies. Overall, knowledge of the effect of nanoparticle size and radiation energy on radiation therapy outcomes could be useful for future applications of Cu-Cy nanoparticles.

Gold nanoparticles are a potential method for enhancing radiation therapy, causing extra damage to tumors when irradiated through the Auger effect. One of the major obstacles to using gold nanoparticles in human trials is the relatively large amount of gold required. This paper details an experiment where a relatively small amount of gold (200 mu g) was used to significantly reduce tumor volume in mice, as well as the results of an inter-tissue biodistribution experiment. Using a longitudinal analysis, tumor size as a function of time was found to be significantly reduced when mice were given 200 mu g of gold nanoparticles and 20 Gray of radiation, compared to radiation alone. 200 mu g in a 20-gram mouse would be mass equivalent to 750 mg of gold in a 75 kg person. Biodistribution measurements demonstrated that gold nanoparticles stayed in the tumor for at least one week after injection when targeted to tumors using pH-Low Insertion Peptide and intratumoral injections. These results show gold nanoparticles to be effective at one of the smallest amounts of gold ever attempted in a mouse, and showed that tumor targeting has the potential to keep gold nanoparticles available in tumors long enough to be beneficial to fractionated radiation treatments (a key component of radiation therapy in the clinic).

Biological indicators would be of use in radiation dosimetry in situations where an exposed person is not wearing a dosimeter, or when physical dosimeters are insufficient to estimate the risk caused by the radiation exposure. In this work, we investigate the use of gene expression as a dosimeter. Gene expression analysis was done on 15,222 genes of Drosophila melanogaster (fruit flies) at days 2, 10, and 20 postirradiation, with X-ray exposures of 10, 1000, 5000, 10,000, and 20,000 roentgens. Several genes were identified, which could serve as a biodosimeter in an irradiated D. melanogaster model. Many of these genes have human homologues. Six genes showed a linear response (R² > 0.9) with dose at all time points. One of these genes, inverted repeat-binding protein, is a known DNA repair gene and has a human homologue (XRCC6). The lowest dose, 10 roentgen, is very low for fruit flies. If the lowest dose is excluded, 13 genes showed a linear response with dose at all time points. This includes 5 of 6 genes that were linear with all radiation doses included. Of these 13 genes, 4 have human homologues and 8 have known functions. The expression of this panel of genes, particularly those with human homologues, could potentially be used as the biological indicator of radiation exposure in dosimetry applications.

In the radiation biodosimetry field, transcriptomic studies seek to determine whether the expression of a small set of genes can be used to estimate the radiation dose that a person was exposed to. Most such studies consider only photon exposure, but in the detonation of an improvised nuclear device, neutrons would likely comprise a significant proportion of the dose. In this study, we compare the effects on gene expression in human blood between two neutron-producing radiation sources: a source designed to mimic the neutron energy spectrum of a nuclear weapon (CINF; the Columbia IND Neutron Facility at the Radiological Research Accelerator Facility) and a source from a nuclear reactor (RINSC; the Rhode Island Nuclear Science Center). The radiation sources have very different neutron energy spectra: mainly fast neutrons (CINF) versus thermal neutrons (RINSC). We have compared differential gene expression at 24 h after exposure to 0, 0.5, 1, 2, and 4 Gy total doses delivered to human blood samples from the same donors in parallel at the two sites. Our analysis suggests that there is a core response to radiation that is conserved at both sites, with larger magnitude and additional components in the CINF response. These results suggest that neutron energy does affect gene expression, and that this must be accounted for in the development of biodosimetry approaches.