Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain). Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension) form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs) with thio-PEG (polyethylene glycol) and thio-glucose, the resulting functionalized GNPs (Glu-GNPs) were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients) was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption over normal cells, different starvation periods were screened in order to achieve optimal treatment effects. Cancer cells were then fed using Glu-GNPs followed by X-ray irradiation treatment. For comparison, solid tumor MCF-7 cells (breast cancer cell line) were studied as well. Our irradiation experimental results show that Glu-GNPs are better irradiation sensitizers to treat THP-1 cells than MCF-7 cells, or Glu-GNPs enhance the cancer killing of THP-1 cells 20% more than X-ray irradiation alone and GNP treatment alone. This finding can help oncologists to design therapeutic strategies to target cancer stem cells and cancer metastasis.

The use of synchrotron light in radiobiological keV x-ray in vitro studies has been accompanied by compromises in culture conditions and sample handling procedures. The presented monochromatic x-ray system bridges the gap between synchrotron science and cell biology by facilitating the irradiation of adherent cells uninterruptedly maintained under cell type-specific conditions throughout the entire experiment. The system for horizontal irradiations consists of a single crystal Laue monochromator, a beam monitor, and a scanning sample stage. As implemented at the BMIT-BM beamline, the system enables homogeneous cell culture irradiations with intense and purely monochromatic x-ray beams (10-30 keV). The first MCF-7 dose-response study demonstrates how the establishment of a stress-minimized experimental procedure leads to accurate and precise in vitro irradiation results. The cell survival as a function of the surface dose is well described by a first-order exponential decay, indicating that the cellular damage induced by 11.9 keV x-rays is comparable to the lethal effects caused by high linear energy transfer particles. The system design opens up the pathway for combined live-cell imaging and monochromatic keV x-ray applications, while the implementation of the system at insertion device beamlines can help to establish novel investigations on the fundamental role of photonactivation agents in an energy regime up to 100 keV.