In vitro test of a potential hypoxic radiosensitizer

Abstract

Oxygen has long been known as a potent radiosensitizer that can enhance the cell killing effects in aerobic cells, while pruned vasculatures and lack of oxygen in the microenvironment of tumor can cause resistance to radiotherapy of cancer. Paradoxically, hypoxia also provides an attractive therapeutic target as it only occurs in solid tumors; hypoxia-activated radiosensitizers may be designed and synthesized with therapeutic selectivity on tumor cells.

Directed by our previous femotomedicine (FMD) mechanistic research, our group has recently discovered a FMD compound that can react with pre-solvated electron (epre) to increase the radiosensitivity in tumor tissues but relatively spare normal tissues. In this thesis work, the in vitro selective radiosensitivity of the FMD compound against hypoxic cancer cells was evaluated through the steady-state absorption spectrum analysis, the immunofluorescence assay, and the clonogenic assay. The results demonstrated that the FMD compound is an effective radiosensitizer in the hypoxic environment (radio enhancement ratio =1.42±0.05 ), and the potency of the radiosensitizing effect of the FMD compound in the oxic (normal) environment will be limited due to the competing attachments of pre-solvated electrons with the FMD molecules and molecular oxygens. The revealing of the underlying mechanism of the FMD compound’s radiosensitizing effect provides new insight into the design of novel hypoxia-activated radiosensitizers.