Radiation Responsive Nanoscale Metal-Organic-Frameworks for Chemoradiation and Molecular Imaging

The utility of radiation from diagnostic imaging to radiotherapy is ubiquitous in modern medicine. In oncology applications, the potential to use nanomaterials to enhance treatment outcomes and enable theranostic approaches is nearing a reality. In our previous work, we have developed a variety of polymeric, inorganic, and composite nanomaterials capable of delivering hydrophilic or hydrophobic chemotherapeutic compounds to cancer cells. Here, we present a metal-organic framework (MOF) nanoparticle platform that serves to interact with X-rays to enhance radiation dose deposition and simultaneously deliver small molecule radiosensitizers and immunomodulating agents. Through incorporation of high-Z elements, such as hafnium, and other compounds that induce ROS generation, we have engineered nanoparticles capable of inducing radiobiological and immunogenic cell death. In colorectal cancer models, the resulting nanoparticles were evaluated for efficacy with regard to tumor control and cell uptake studies by in vivo CT and TEM analysis of harvested tissues. In addition, formulations of lanthanide containing MOFs were evaluated in novel X-ray based techniques, radioluminescent imaging and spectral photon counting CT. Overall, these results provide a strong foundation for the further development of this nanomedicine platform.