Hypoxia is recognized as a major factor contributing to radioresistance, and in prostate cancer, is directly associated with shorter times to biochemical relapse and metastasis. Radiation therapy generates radical DNA species that are readily reversible under hypoxic conditions; however, oxygen chemically fixes this damage by oxidizing the DNA radicals to yield peroxides that ultimately result in DNA strand breaks and cell death. This renders hypoxic tumors ~3x more resistant to radiation than well oxygenated ones. Attempts to improve tumor oxygenation by altering the oxygen carrying capacity of blood (i.e. hyperbaric oxygen, respiratory hyperoxia, and carbogen, hemoglobin-based agents and perfluorocabon based emulsions) have had limited success in various clinical trials, and is most likely due to an abnormal tumor microenvironment. Our laboratory has pioneered the fabrication of polymer-shelled hollow microparticles (PHMs) that can rapidly load and release concentrated oxygen at controlled rates in response to changes in the partial pressure of the surrounding fluid. We are interested in using these systems to actively reverse tumor hypoxia during radiotherapy.