Project Summary Metastasis accounts for over 90% of all cancer associated suffering and death, and arguably presents the most formidable challenges in cancer management. The central innovation and overall goal of this project is the development of new design radiotherapy biomaterials that could be employed to significantly boost pancreatic/lung/prostate cancer cure rate: including treatment of metastasis and overcoming radioresistance, all at no additional inconvenience to patients. The new biomaterials are designed to simply replace the inert biomaterials (fiducials/spacers), which are currently routinely implanted to ensure spatial accuracy during radiotherapy. These new biomaterials specifically incorporate a payload of non-toxic targeted radiosensitizing gold nanoparticles (GNP), and immunoadjuvants in a biodegradable polymer matrix. Once in place, the new design biomaterials controllably release the payload directly into the tumor as the polymer degrades. During radiotherapy, the released GNP will significantly enhance local tumor cell kill, substantially boosting dose to radioresistant tumor cells via Einstein?s photoelectric effect, with minimal toxicity to healthy tissue. Meanwhile, antigens from irradiated tumor cells work with the released immunoadjuvant to prime a robust T cell response, which may kill metastatic cells distant from the irradiated site (abscopal effect) and establish immune memory to prevent cancer recurrence. Slow in-situ release of the payload will minimize systemic/overlapping toxicities, which are currently a critical barrier/concern with competing approaches. Overall, our low risk, potential high-reward innovation could significantly enhance survival and quality of life for pancreatic/ung/prostate cancer patients.