Photodynamic therapy (PDT), a treatment that uses a photosensitizer, molecular oxygen, and light to kill target cells, is a promising cancer treatment method. However, a limitation of PDT is its dependence on light that is not highly penetrating, precluding the treatment of tumors located deep in the body. Copper-cysteamine nanoparticles are a new type of photosensitizer that can generate cytotoxic singlet oxygen molecules upon activation by X-rays. In this paper, we report on the use of copper-cysteamine nanoparticles, designed to be targeted to tumors, for X-ray–induced PDT. In an in vivo study, results show a statistically significant reduction in tumor size under X-ray activation of pH-low insertion peptide–conjugated, copper-cysteamine nanoparticles in mouse tumors. This work confirms the effectiveness of copper-cysteamine nanoparticles as a photosensitizer when activated by radiation and suggests that these Cu-Cy nanoparticles may be good candidates for PDT in deeply seated tumors when combined with X-rays and conjugated to a tumor-targeting molecule.
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.
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.
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