Biogeochemistry concepts in medicine: Radiosensitizing pancreatic cancer through pathology driven biosynthesis of gold nanoparticles.

An effective strategy for overcoming radiotherapy resistance is to sequester radiosensitizing hafnium oxide or gold nanoparticles (GNPs) within tumors, but desmoplasia, but desmoplasia creates a delivery barrier impeding this approach. Here we report a radiosensitization strategy that overcomes this limitation by applying an atomic-scale agent - ionic gold - for in situ biosynthesis of GNPs within tumors. We showed that the in situ generation of GNPs occurs with higher efficiency in cancerous pancreatic cells than in non-cancerous cells and that these GNPs have high nuclear localization, resulting in the specific radiosensitization of cancer cells. Our studies in a xenograft murine model of pancreatic cancer revealed a uniform distribution of GNPs in the tumor, with insignificant gold content and low toxicity in normal organs. Radiosensitization by biosynthesized GNPs halted tumor growth for more than 30 days and was associated with a significantly higher median survival versus radiation alone (235 vs 102 days, respectively).