Auger electrons and DNA double-strand breaks studied by using iodine-containing chemicals.

Irradiation of high Z elements such as iodine, gold, gadolinium with monochromatic X-rays causes photoelectric effects that include the release of Auger electrons. Decay of radioactive iodine such as I-123 and I-125 also results in multiple events and some involve the generation of Auger electrons. These electrons have low energy and travel only a short distance but have a strong effect on DNA damage including the generation of double-strand breaks. In this chapter, we focus on iodine and discuss various studies that used iodine-containing chemicals to generate Auger electrons and cause DNA double-strand breaks. First, DNA synthesis precursors containing iodine were used to place iodine on DNA. DNA binding dyes such as iodine Hoechst were investigated for Auger electron generation and DNA breaks. More recently, iodine containing nanoparticles were developed. We describe our study using tumor spheroids loaded with iodine nanoparticles and synchrotron-generated monochromatic X-rays. This study led to the demonstration that an optimum effect on DNA double-strand break formation is observed with a 33.2keV X-ray which is just above the K-edge energy of iodine.

Uranium chelating ability of decorporation agents in serum evaluated by X-ray absorption spectroscopy.

Internal exposure to actinides such as uranium and plutonium has been reduced using chelating agents for decorporation because of their potential to induce both radiological and chemical toxicities. This study measures uranium chemical forms in serum in the presence and absence of chelating agents based on X-ray absorption spectroscopy (XAS). The chelating agents used were 1-hydroxyethane 1,1-bisphosphonate (EHBP), inositol hexaphosphate (IP6), deferoxamine B (DFO), and diethylenetriaminepentaacetate (DTPA). Percentages of uranium-chelating agents and uranium-bioligands (bioligands: inorganic and organic ligands coordinating with uranium) dissolving in the serum were successfully evaluated based on principal component analysis of XAS spectra. The main ligands forming complexes with uranium in the serum were estimated as follows: IP6 > EHBP > bioligands > DFO ≫ DTPA when the concentration ratio of the chelating agent to uranium was 10. Measurements of uranium chemical forms and their concentrations in the serum would be useful for the appropriate treatment using chelating agents for the decorporation of uranium.

Iodine containing porous organosilica nanoparticles trigger tumor spheroids destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge energy X-ray.

X-ray irradiation of high Z elements causes photoelectric effects that include the release of Auger electrons that can induce localized DNA breaks. We have previously established a tumor spheroid-based assay that used gadolinium containing mesoporous silica nanoparticles and synchrotron-generated monochromatic X-rays. In this work, we focused on iodine and synthesized iodine-containing porous organosilica (IPO) nanoparticles. IPO were loaded onto tumor spheroids and the spheroids were irradiated with 33.2 keV monochromatic X-ray. After incubation in CO2 incubator, destruction of tumor spheroids was observed which was accompanied by apoptosis induction, as determined by the TUNEL assay. By employing the γH2AX assay, we detected double strand DNA cleavages immediately after the irradiation. These results suggest that IPO first generate double strand DNA breaks upon X-ray irradiation followed by apoptosis induction of cancer cells. Use of three different monochromatic X-rays having energy levels of 33.0, 33.2 and 33.4 keV as well as X-rays with 0.1 keV energy intervals showed that the optimum effect of all three events (spheroid destruction, apoptosis induction and generation of double strand DNA breaks) occurred with a 33.2 keV monochromatic X-ray. These results uncover the preferential effect of K-edge energy X-ray for tumor spheroid destruction mediated by iodine containing nanoparticles.

Studies on the Exposure of Gadolinium Containing Nanoparticles with Monochromatic X-rays Drive Advances in Radiation Therapy.

While conventional radiation therapy uses white X-rays that consist of a mixture of X-ray waves with various energy levels, a monochromatic X-ray (monoenergetic X-ray) has a single energy level. Irradiation of high-Z elements such as gold, silver or gadolinium with a synchrotron-generated monochromatic X-rays with the energy at or higher than their K-edge energy causes a photoelectric effect that includes release of the Auger electrons that induce DNA damage-leading to cell killing. Delivery of high-Z elements into cancer cells and tumor mass can be facilitated by the use of nanoparticles. Various types of nanoparticles containing high-Z elements have been developed. A recent addition to this growing list of nanoparticles is mesoporous silica-based nanoparticles (MSNs) containing gadolinium (Gd-MSN). The ability of Gd-MSN to inhibit tumor growth was demonstrated by evaluating effects of irradiating tumor spheroids with a precisely tuned monochromatic X-ray.

Destruction of tumor mass by gadolinium-loaded nanoparticles irradiated with monochromatic X-rays: Implications for the Auger therapy.

Synchrotron generated monochromatic X-rays can be precisely tuned to the K-shell energy of high Z materials resulting in the release of the Auger electrons. In this work, we have employed this mechanism to destruct tumor spheroids. We first loaded gadolinium onto the surface of mesoporous silica nanoparticles (MSNs) producing gadolinium-loaded MSN (Gd-MSN). When Gd-MSN was added to the tumor spheroids, we observed efficient uptake and uniform distribution of Gd-MSN. Gd-MSN also can be taken up into cancer cells and localize to a site just outside of the cell nucleus. Exposure of the Gd-MSN containing tumor spheroids to monochromatic X-ray beams resulted in almost complete destruction. Importantly, this effect was observed at an energy level of 50.25 keV, but not with 50.0 keV. These results suggest that it is possible to use precisely tuned monochromatic X-rays to destruct tumor mass loaded with high Z materials, while sparing other cells. Our experiments point to the importance of nanoparticles to facilitate loading of gadolinium to tumor spheroids and to localize at a site close to the nucleus. Because the nanoparticles can target to tumor, our study opens up the possibility of developing a new type of radiation therapy for cancer.