UC Davis

X-ray is widely used in medical areas, typically for cancer treatment. Studies seek to enhance the X-ray effect using nanomaterials to increase energy deposition efficiency and a new discipline called X-ray nanochemistry was established based on these studies. While nanoparticles with high Z materials are proven to be able to deposit more X-ray energy to a system, nanoparticles are also found to be involved in the chemical reactions triggered by X-ray or biological response under radiation. These findings lead to discussions about other types of dose enhancement factors like chemical enhancement and biological enhancement are discussed. More studies were still needed to study the mechanisms and deconvolute these dose enhancement factors. The dissertation presents continuous work in the field of X-ray nanochemistry, focusing on type 2 physical enhancement and chemical enhancement. Direct quantification of type 2 physical enhancement (T2PE) was done by conjugating a 12-mer single-strand DNA onto surfaces of silica-coated gold nanoparticles (Au@SiO2). T2PE comes from energy deposited by secondary electrons emitted from nanoparticles in radiation which are low-energy electrons and will disappear a few nanometers from the surface of the nanoparticles. 3 reporters were linked to DNA strands respectively and the magnitude of T2PE was determined by comparing the number of reporters released from Au@SiO2 versus the same size of SiO2 when DNA strand breaks occurred. More than 9 times more reporters were released in the presence of 1wt% Au@SiO2. T2PE showed a much higher dose enhancement factor than T1PE and can help to develop X-ray-triggered releasing nanosystems by using single-strand DNA as linkers on the nanoparticle surface. An EPR study was performed using spin trap BMPO(5-tert-Butoxycarbonyl-5-methyl-1-pyrroline-N-oxide) to detect •OH produced by X-ray radiation in the presence of 3-nm THPC (Tetrakis(hydroxymethyl)phosphonium chloride) AuNPs. Similar amounts of •BMPO-OH, the intermediate, were detected compared to the solution irradiated without the presence of AuNPs. More •BMPO-H adduct was detected when AuNPs were in the solution during radiation. Such a result indicated that for low concentration of small AuNPs didn’t increase the production of •OH but catalyzed the conversion of a hydroxylation intermediate to another product. A triple jumps mechanism was then proposed based on this finding. The possible existence of catalyzed breakage of single-strand DNA on small AuNPs surfaces was explored. DNA strands with fluorophores and quenchers at each end were loaded on Au surfaces then irradiated. The FRET (Förster resonance energy transfer) effect on the DNA strand was interrupted when the strand is broken. Amounts of SSBs (single-strand breaks) were determined using increased fluorescence intensity after X-ray irradiation. Mass spectrometry was used to quantify DNA damage after irradiation using an internal standard in the samples. Nearly 9 times more SSBs with correction when DNA strands were on 5-nm citrate AuNPs. A higher SSBs to total DNA damage ratio was also found, indicating possible catalytic base damage conversion to strand breaks on Au surfaces. A nanoreactor for X-ray application was synthesized and tested. A •OH probe, 3CCA (coumarin-3-carboxylic acid) was encapsulated in hollow mesoporous silica shells. The shells were sealed with another layer of solid silica to prevent probes from escaping. A dose-dependent response was measured with fluorometry. A linear dose response was observed when the nanoreactors were in dry form or suspended in solutions with scavengers or with small AuNPs. Results showed that the synthesized structure can be used as a nanoreactor for X-ray application. The silica layer was not interacting with probes trapped inside and successfully isolated internal molecules.